Article Category: Research

Tumor Markers May Help Doctors Decide Which Head and Neck Cancer Patients Need Immunotherapy Before Surgery

WashU Medicine physician-scientists at Siteman Cancer Center identify a promising way to help guide immunotherapy treatment decisions and enhance patient care

Building upon more than a decade of investigator-initiated clinical trials at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, researchers have identified a malignant cell biomarker that may predict which patients will respond to the immunotherapy drug pembrolizumab, known commercially as Keytruda, for the treatment of resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC).

The research, published March 31 in Cell Reports Medicine, is the latest discovery from one of the nation’s leading head and neck tumor centers, the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center. The findings point to a cell surface protein, major histocompatibility complex class II (MHC-II), as the tumor marker that may help guide treatment decisions. It is typically expressed on immune cells and is important for activating immune responses in the body.

In the study, the researchers found that malignant cells expressing MHC-II and interferon response genes respond better to pembrolizumab administered before surgery, suggesting that a malignant-interferon (IFN)/MHC-II program could be developed into a genomic test to stratify patients into those who should proceed with immunotherapy before surgery and those who should proceed directly to surgery and not be given immunotherapy beforehand.

“Patients with advanced head and neck cancer often undergo immunotherapy prior to and after surgery,” said Sidharth V. Puram, MD, PhD, the Lindburg Professor of Otolaryngology and chair of the Department of Otolaryngology — Head & Neck Surgery at WashU Medicine and co-director of the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center. “The use of immunotherapy drugs, however, means that surgery is delayed by as much as eight to 10 weeks. If we can determine which patients are more likely to benefit from immunotherapy and which ones should go straight to surgery, we can potentially improve overall outcomes for our patients. We think that’s what (IFN)/MHC-II can do: predict how well patients will have a tumor response to immunotherapy.”

Puram is the corresponding author of the study. Co-senior authors are Douglas R. Adkins, MD, director of the Section of Head and Neck and Thyroid Medical Oncology in the Division of Medical Oncology at WashU Medicine and co-director of the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman; Ravindra Uppaluri, MD, PhD, director of Head and Neck Surgical Oncology at Dana-Farber Cancer Institute; and Itay Tirosh, PhD, senior scientist in the Department of Molecular Biology at the Weizmann Institute of Science in Israel.

WashU Medicine researchers already have defined a new standard for the treatment for resectable LA-HNSCC in adults. In the pivotal global KEYNOTE-689 Phase 3 clinical trial, published in the New England Journal of Medicinein June 2025 and co-led by Adkins and Uppaluri, researchers found that the administration of pembrolizumab before and after surgery combined with adjuvant (chemo) radiation therapy resulted in tumor cell death in the surgical specimen and significantly improved the event-free survival (EFS) for these patients.

Perioperative pembrolizumab was approved by the FDA in June 2025 and changed the standard treatment pathway for patients with LA-HNSCC.

“The KEYNOTE-689 trial was built on the favorable results of investigator-initiated trial testing of perioperative pembrolizumab that was developed and conducted at WashU Medicine (with participating sites at the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center),” Adkins said. “In these trials, administration of pembrolizumab before surgery resulted in evidence of tumor cell death in the surgical specimen in up to 50% of patients, a finding linked to better EFS. However, a biomarker was needed that could predict which patients benefited from pembrolizumab before the immunotherapy drug was given. Tumor PD-L1 protein expression does predict potential benefit with pembrolizumab in these patients; however, this test is a very weak predictive biomarker. Predictive biomarkers with stronger links to benefit with pembrolizumab are needed to select patients a priori who may or may not benefit from pembrolizumab before and after surgery.”



To understand the underlying biology and what might drive tumor responses to immunotherapy, researchers used single-cell RNA-sequencing on tissue samples from 16 HNSCC patients, both pre- and post-neoadjuvant pembrolizumab treatment, who were enrolled in the phase 2 trials that represent the predecessors to KEYNOTE-689.



“Single cell approaches allowed us to profile the individual malignant cells and understand the specific genes expressed and how they change with immunotherapy,” Puram said. “Surprisingly, we found a subpopulation of malignant cells that were defined by MHC-II and interferon response genes that predicted immunotherapy response.”



The researchers believe that MHC-II and interferon expression by malignant cells reflects engagement of immune cells with T cells, which are positioned to kill the cancer but have been “turned off” — a state called T-cell exhaustion. Based on spatial techniques, they hypothesize that immunotherapy drugs like pembrolizumab “wake up” these T cells, with MHC-II and interferon identifying which tumors might be poised to then respond to the immunotherapy.



“These results suggest that for the first time, a clinically available strong predictive biomarker may become available to clinicians that can be used to decide whether to include perioperative pembrolizumab before and after surgery and adjuvant therapy for the treatment of patients with LA-HNSCC,” Adkins said. “This will be an important milestone to achieve for our patients.”



“What we’ve demonstrated is the importance of malignant cell states for immunotherapy response,” Puram added. “After more studies with more patients, we envision that a simple test could be developed that tells us if a patient expresses (IFN)/MHC-II and therefore would benefit from immunotherapy. We think this is a significant finding as we continuously try to predict which patients will respond and how to make treatments more effective.”

Historical Clinical and Research Breakthroughs

Siteman Cancer Center has a long history of improving outcomes and driving novel research into head and neck cancers. The WashU Medicine Department of Otolaryngology is among the top 10 recipients of NIH research funding among otolaryngology departments. Within the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center, investigators and physician-scientists across a multidisciplinary team of otolaryngology, medical oncology and radiation oncology specialists oversee one of the largest basic, translational and clinical research portfolios in the country. In addition to paradigm-changing clinical trials such as the KEYNOTE-689 trials, researchers at the center have pioneered advanced reconstructive techniques and new therapies with radiation and chemotherapy, as well as immunotherapies and targeted therapies for head and neck cancers.

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Innovative CAR-T cell therapy receives FDA breakthrough therapy designation

Immunotherapy for aggressive T-cell cancers developed by WashU Medicine researchers moves to faster approval pathway

A cell-based immunotherapy designed to treat rare and aggressive types of blood cancer has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA). Developed by researchers at Washington University School of Medicine in St. Louis, this innovative CAR-T cell therapy is licensed to Wugen, a WashU Medicine startup biotechnology company based in St. Louis’ Cortex Innovation District.

The immunotherapy was developed by WashU Medicine physician-scientists who treat patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine.

The therapy — called WU-CART-007 (soficabtagene geleucel) — targets specific blood cancers called T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL). These are aggressive forms of blood cancer that originate in the immune system’s T cells, a type of white blood cell important for the body’s immune response. These cancers often don’t respond at all to standard care or return after several rounds of treatment, leaving patients with few treatment options and poor prognoses. Stem cell transplantation is the only curative treatment for such cancers, but these patients rarely qualify for it because they must first achieve remission following early rounds of chemotherapy, which is rare for these blood cancers.

The FDA’s Breakthrough Therapy designation aims to speed up the development and regulatory review of treatments for serious or life-threatening conditions, especially therapies that may offer substantial improvements over existing options. The Breakthrough Therapy designation for Wugen’s immunotherapy is based on preliminary clinical evidence showing early success in treating these aggressive blood cancers. Early-phase clinical studies have demonstrated that the therapy can selectively target and eliminate cancerous T cells with manageable side effects.

About 1,000 people are diagnosed with T-cell cancers each year in the U.S. If the cancer does not respond to treatment or returns after initial treatment, patients survive an average of six months, and fewer than 7% are still living at the five-year mark.

“This therapy has the potential to enable long-term survival for this patient population by controlling the disease and allowing patients — who would otherwise not be eligible — to proceed to stem cell transplantation, the only potentially curative treatment for these blood cancers,” said WashU Medicine oncologist John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine and director of WashU Medicine’s Center for Gene and Cellular Immunotherapy, who first developed the therapy in his lab at WashU Medicine. “We remain hopeful that the ongoing Phase 2 study will be completed soon, and we’ll have positive results — but we’ll need some time to see how the patients do in both short-term and long-term follow-up.”

DiPersio treats patients at Siteman Cancer Center and founded Wugen alongside other WashU Medicine investigators, including Matthew Cooper, PhD, who then was on the WashU Medicine faculty and now serves as Wugen’s chief scientific officer. The researchers worked with WashU’s Office of Technology Management (OTM) to launch the company in 2018.

The early-phase clinical trial that led to the Breakthrough Therapy designation was conducted in multiple study centers in the U.S., Australia and Europe. The Phase 1 study included 28 adult and adolescent patients with either T-cell lymphoblastic cancer that returned after several lines of therapy or that never responded to treatment. Of 11 patients who could be evaluated after treatment, the overall response rate was 91%, meaning 10 patients either showed no signs of cancer after treatment or their cancer cell burden was reduced significantly. Eight out of 11 patients (72.7%) achieved complete remission. At the study’s data cutoff, six who underwent a transplant remained in remission, with no evidence of disease six to 12 months later, according to the study published in the journal Blood.

“This FDA Breakthrough Therapy designation for soficabtagene geleucel highlights the role of Siteman Cancer Center, a leading NCI-designated Comprehensive Cancer Center, and WashU Medicine in advancing innovative CAR-T cell therapies for aggressive T-cell leukemias and lymphomas,” said Timothy J. Eberlein, MD, director of Siteman Cancer Center and the Spencer T. and Ann W. Olin Distinguished Professor at WashU Medicine. “The dedicated work of our physician-scientists and clinicians is translating the most cutting-edge cellular immunotherapy research into the newest treatment options for patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.”

The phase 2 trial is currently ongoing. At the Siteman site, the clinical trials have been led by principal investigator Armin Ghobadi, MD, a professor of medicine, director of cellular therapies at Siteman, and clinical director of WashU Medicine’s Center for Gene and Cellular Immunotherapy. Siteman Kids at St. Louis Children’s Hospital and WashU Medicine is a key site for the pediatric portion of the clinical trial, co-led by Thomas Pfeiffer, MD, an assistant professor of pediatrics. Ghobadi and Pfeiffer have no financial interest in Wugen.

A major advantage of the treatment is its “off-the-shelf” availability, eliminating the need to manufacture an individualized cell product for each patient. The cell therapy can be prepared in advance from cells donated by healthy individuals and used to treat any patient with a T-cell cancer. In contrast, already-approved CAR-T cell therapies are adapted from the patient’s own immune cells, a process that typically takes three to four weeks. The accelerated treatment timeline of the Wugen immunotherapy reduces logistical and financial barriers associated with most cell-based therapies. This speed can make a meaningful difference because it is not unusual for patients with these aggressive cancers to die while waiting for the therapeutic cells to be prepared.

These particular blood cancers present a unique challenge because the therapeutic cells and the cancer cells are both T cells, so DiPersio and his colleagues came up with further innovations to prevent the therapeutic T cells from mistaking one another for the cancer and causing CAR-T cell fratricide. All other approved CAR-T cell therapies target B cell cancers, which do not have this T cell self-targeting complication.

Grant furthers novel therapeutic approach to glioblastoma

Mosquito-borne Zika virus helps destroy deadly brain cancer in mice

Milan G. Chheda, MD, an associate professor of medicine in the Division of Oncology at WashU Medicine and a brain tumor specialist at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, has received a nearly $1.5 million grant from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.

The three-year award will significantly advance a unique viral-based immunotherapy for glioblastoma, a lethal brain cancer that typically results in death within two years.

Chheda’s research repurposes the Zika virus, which has been linked to neurological adverse events. Instead, Chheda and colleagues engineered and tested the virus to selectively target and destroy glioblastoma tumor cells while sparing healthy brain tissue. The virus has proven highly effective in mice, giving a powerful boost to an immunotherapy drug and training the immune system to surveil and prevent against recurrence. The Kleberg Foundation award is essential for sustaining momentum, allowing Chheda and his team to complete key work needed to transition to a first-in-human clinical trial. Chheda previously received a Kleberg Foundation grant in 2017 to support this work.

Glioblastoma is the most common and aggressive form of brain cancer. About 12,000 people are diagnosed each year in the U.S.

Chheda also is director of neuro-oncology at WashU Medicine and a physician-scientist and associate director at The Brain Tumor Center at Siteman.

FDA Breakthrough Therapy Designation Reflects Practice-Changing Trends Only at Siteman

Recognition follows strong early clinical results for a novel off-the-shelf CAR T therapy targeting rare and aggressive T-cell malignancies

A novel off-the-shelf CAR T-cell therapy pioneered at Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine is gaining national recognition after delivering striking clinical results in patients with rare and aggressive blood cancers.

The FDA has granted Breakthrough Therapy Designation to WU-CART-007, an allogeneic anti-CD7 CAR T-cell therapy developed by WashU Medicine researchers. In early global trials, 73% of adults and adolescents with relapsed or refractory (R/R) T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma (T-ALL/LBL) achieved full remission following treatment — an outcome that positions the therapy as a potential gamechanger in T-cell malignancies.

“Relapsed T-cell leukemias and lymphomas represent one of the most challenging areas in hematologic oncology,” said oncologist John DiPersio, MD, PhD, director of the Center for Gene and Cellular Immunotherapy at WashU Medicine and an internationally recognized cell therapy leader at Siteman Cancer Center. “We are leading transformative advances for patients with these rare and aggressive cancers. Developing an off-the-shelf CAR T platform that can induce high remission rates in this population reflects the translational depth and cellular therapy infrastructure we’ve built at Siteman.”

DiPersio and Matthew Cooper, PhD, developed the therapy — manufactured using an off-the-shelf approach from healthy donors — to target CD7+ malignancies. The two founded the biotech company Wugen in 2018 to advance the research. Further clinical trials are underway in the U.S., Europe, Asia and Australia, including at Siteman Cancer Center and Siteman Kids at St. Louis Children’s Hospital.

In reviewing results from earlier clinical trials in children, researchers at Siteman Kids noted that WU-CART-007 (also known as soficabtagene geleucel, or sofi-cel) could be a gamechanger if the therapy continues to move almost all patients from disease-state to remission, thus enabling patients to undergo stem cell transplantation.

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‘An Eco-System of Innovation and Excellence’

The rapid advance of WU-CART-007 is just the latest example of what Timothy J. Eberlein, MD, director of Siteman Cancer Center, says arises out of a robust eco-system of innovation, collaboration and excellence in cancer research at WashU Medicine.

Siteman is known internationally for its basic and translational research efforts and is one of only a few institutions to receive three prestigious Specialized Program of Research Excellence (SPORE) grants from the National Cancer Institute (NCI), for leukemia, endometrial and pancreatic cancer research.

Blood Cancer United, formerly known as the Leukemia & Lymphoma Society, also has awarded scientists at Siteman a Specialized Center of Research (SCOR) grant for lymphoma research. Such grants are specifically designed to accelerate promising translational research into patient care.

“We are committed to continually advancing treatments for cancer and broadening options for patients,” Eberlein said. “Toward that goal, we have initiated several home-grown clinical trials that have changed the course of treatment for many cancers. Our depth and breadth of oncology research is wide, and our expertise is the result of innovation, dedication and multidisciplinary cross-collaboration that occurs throughout our center.”

Other examples of comprehensive, specialized programs at Siteman include the:

Translational Research Highlights

In addition to the latest breakthrough in leukemia and lymphoma research and care, examples of other research efforts that have changed practice guidelines include:

  • New Standard of Care Established for Locally Advanced Head and Neck Cancers — In the first change in standard-of-care therapy in more than 20 years, the FDA approved the use of the immunotherapy drug pembrolizumab (Keytruda) for treatment of resectable locally advanced head and neck squamous cell carcinoma (HNSCC) in adults. The approval, announced in mid-2025, came after a clinical trial initiated at Siteman in 2013. That trial and later ones, including an international trial, demonstrated greater tumor shrinkage prior to surgery and longer survival rates when immunotherapy was added. “It’s exciting to see our ideas move toward clinical practice with such impressive and potentially life-changing results,” said Douglas Adkins, MD, co-director of the Head and Neck Tumor Center at Siteman, who co-led the clinical trials at Siteman and elsewhere.
  • Addition of Brentuximab Vedotin for Relapsed Diffuse Large B-Cell Lymphoma Results in Statistically Significant Survival Benefit — With approximately 40% of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) having relapsed or refractory disease, researchers at Siteman, led by Nancy Bartlett, MD, found in the ECHELON-Phase Three clinical trial that the use of an antibody-drug conjugate brentuximab vedotin, when combined with either lenalidomide or rituximab, was not only safe but also demonstrated improved survival benefit in patients with R/R DLBCL.
  • Dostarlimab Plus Chemo for Primary Advanced or Recurrent Endometrial Cancer — Matthew Powell, MD, co-led national studies that found adding immune checkpoint inhibitors to standard therapy for endometrial cancer improves outcomes for many patients, with an average increase in overall survival of 31%.
  • T-cell Immunotherapy Effective in Treating Rare Soft Tissue Cancers — Siteman Cancer Center’s Sarcoma program was a major clinical trial site for this study, which found that T-cell immunotherapy, specifically the drug afamitresgene autoleucel, or afami-cel, was effective and generated long-term responses in patients with rare soft tissue cancers.
  • Sotorasib Approved as Targeted Therapy for Patients with Specific Type of Non-Small-Cell Lung Cancer — Following clinical trials at Siteman and globally, the FDA approved sotorasib for patients with non-small-cell lung cancer whose tumors express a G12C mutation in the KRAS gene and who have already undergone previous treatment. Ramaswamy Govindan, MD, who led the study, noted that the drug targeted the most common mutation, reduced tumor sizes, and improved overall survival rates.
  • Medicare Approves Whole-Genome Test for Blood Cancers — A test for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) developed at Siteman was the first whole-genome sequencing test for cancer to be approved for reimbursement by the Centers for Medicare & Medicaid Services. Called ChromoSeq, the test is now routinely used by oncologists to guide treatment decisions for patients with blood cancers.

“At Siteman, we have built one of the world’s leading cellular immunotherapy programs focused on developing next-generation treatments for rare and refractory cancers,” Eberlein said. “Many of our most impactful cell therapy trials are investigator-initiated and originated here, reflecting a translational infrastructure designed to bring innovative therapies to patients with the most aggressive and rarest cancers.”

Siteman Cancer Center announces 2026 American Cancer Society-funded pilot projects

WashU Medicine grant recipients will focus on lung and blood cancers

Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, is pleased to announce the next cohort of pilot projects funded by the Institutional Research Grant from the American Cancer Society. The three projects are described below.

Jason Weber Phd
Jason Weber, PhD

Under the leadership of Jason Weber, PhD, who has been principal investigator of the grant since 2011, these awards support independent, self-directed investigators early in their careers and enable them to conduct research in areas of special interest to the American Cancer Society.

WashU has funded early-career oncology researchers with this grant since 1958. Learn about projects initially supported in 2022, 2023, 2024 and 2025.

Project Title: Complement Modulation as a Strategy to Sensitize Tumors to Radiotherapy

Radiotherapy Principal Investigator: Vaishali Kapoor, PhD

Vaishali Kapoor, PhD
Vaishali Kapoor, PhD

Summary: Lung cancer is the leading cause of cancer-related deaths in the U.S., and non-small cell lung cancer (NSCLC) accounts for about 85% of all cases. Radiation therapy (RT) is one of the most common and effective treatments for NSCLC, used in combination with chemotherapy and immunotherapy. While many patients initially respond to RT, most eventually experience cancer recurrence. One reason for treatment failure is that tumors can change their surrounding environment to hide from the immune system and resist therapy. This research focuses on the complement system, a part of the body’s natural immune defense, which helps recognize and destroy harmful cells. Surprisingly, new evidence suggests that in cancer, activation of the complement system can have the opposite effect: Instead of helping the immune system, it may help tumors survive. Researchers have found that RT activates the complement system, releasing a molecule called C3a, which then signals through a receptor called C3aR to recruit cells that suppress the immune system. At the same time, RT generates another molecule called iC3b, which programs certain immune cells to become less effective at fighting cancer. In this project, the researchers will investigate how these processes occur and test whether blocking C3aR — using a drug that already exists — can reprogram the immune system, allowing it to work together with RT to fight cancer more effectively. The long-term goal is to develop new combination therapies that enhance the power of RT, make immunotherapies more effective and improve survival for patients with lung cancer.

Project Title: Glycan-Guided Pathomic Signatures of Immunotherapy Response in Non-Small Cell Lung Cancer

Principal Investigator: José Marcio Luna, MS, PhD

José Marcio Luna, MS, PhD
José Marcio Luna, MS, PhD

Summary: A type of treatment called immunotherapy has transformed care for some patients with advanced lung cancer by helping the immune system recognize and attack cancer cells. Unfortunately, this treatment does not work for everyone, and doctors currently lack reliable ways to know in advance which patients will benefit. As a result, many patients are exposed to treatments that may not help them while losing valuable time for other therapies. Researchers will explore whether patterns inside tumor tissue can help predict which patients are most likely to respond to immunotherapy. They will use lung tissue samples that were already collected from patients treated by WashU Medicine physicians. With the help of advanced imaging techniques, the researchers can map molecules such as sugars and proteins within the tumor. These maps will then be linked to digital images of the same tissue under the microscope. By analyzing these images with computer algorithms, scientists can detect subtle patterns that are invisible to the human eye. The goal of this work is to identify new patterns in tumor tissue that indicate whether a patient will respond well to immunotherapy. If successful, this approach could improve the way doctors select treatments for lung cancer, ensuring patients receive therapies that are most likely to help them. In the future, this research may also open the door to better tests that can guide treatment decisions for many other types of cancer.

Project Title: Germline Genome Sequencing in Patients with Myeloid Neoplasms in Paraguay

Principal Investigator: Samuel Urrutia, MD, MS

Samuel Urrutia, MD, MS
Samuel Urrutia, MD, MS

Summary: This study is about understanding what causes myeloid neoplasms, a type of blood cancer, in a diverse population in Paraguay. While treatments for these cancers have improved in high-income countries, they’re often not available in places like Paraguay. A project called GEMA is already underway there, using advanced genetic testing to diagnose these cancers. This new project, an expansion of GEMA, aims to go a step further. It will look at two main things. First, it will search for inherited genetic changes (germline variants) that make people more susceptible to these cancers and see how they interact with new genetic changes (somatic alterations) that happen later in a person’s life. Second, the study will investigate how a person’s genes and their environment (gene-environment interaction) might work together to cause these cancers. To do this, researchers will analyze genetic information from saliva samples collected from patients. By combining this new information with data on their ancestry, environment and the genetic changes in their cancer cells, the study’s researchers hope to get a complete picture of why these cancers develop in this specific population. Ultimately, the goal is to identify new risk factors and better understand the unique challenges faced by patients with myeloid neoplasms in Latin America, which could lead to more effective prevention and treatment strategies in the future.

New imaging approach reduces unnecessary breast biopsies by nearly 25%

WashU researchers at Siteman Cancer Center are advancing breast imaging to help patients avoid invasive procedures and improve the screening experience

In a new discovery at Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine, a team of researchers and physicians found that utilizing ultrasound-guided diffuse optical tomography technology can reduce unnecessary breast biopsy rates by nearly 25%.

Now for the first time in a clinical trial, Siteman Cancer Center is using these new methods first, rather than starting with a biopsy, to determine if additional diagnoses are needed to test for cancer. The research was recently published in Breast Cancer Research and supported by a nearly $2 million grant from the National Cancer Institute of the National Institutes of Health.

Every year in the United States, more than 1 million breast biopsies are performed. Yet 75-80% of those biopsies turn out to be benign, meaning patients undergo an invasive procedure, anxiety, and waiting — only to learn cancer is not present.

New Research in Breast Cancer Imaging

In a double-blind clinical trial involving 226 patients, the WashU Medicine research and physician team at Siteman found that ultrasound-guided diffuse optical tomography (DOT) — used alongside standard breast ultrasound — can reduce unnecessary benign biopsies by nearly 25%, while maintaining a false negative rate below 2%, consistent with American College of Radiology safety standards.

By combining standard ultrasound with diffuse optical tomography, radiologists gain additional information about tissue biology, not just structure.

Why This Matters for Patients Undergoing Breast Imaging

A biopsy remains the only way to definitively diagnose breast cancer. However, many suspicious findings on mammography or ultrasound are not cancer — and the uncertainty between imaging and biopsy can be one of the most stressful periods in a patient’s experience.

This research aims to improve how physicians distinguish which lesions truly require biopsy and which may be safely monitored. For patients, it means care that is not only the most advanced but thoughtfully designed to ensure that cancer is detected as early and screening is as accessible and low-cost as possible for more people.

Leadership in Breast Imaging Innovation

The study was led by:

Their multidisciplinary team included experts in radiology, pathology, engineering and clinical research across Siteman and WashU:

The study team also included Steven P. Poplack, MD, formerly of WashU Medicine and Siteman, who is now a professor of radiology (breast imaging) at Stanford University.

# # #

Zhu Q, Bennett D, Hagemann IS, Mannix J, Wiele K, Luther M, Luo J, Poplack SP. Ultrasound-guided diffuse optical tomography: An adjunct to ultrasound that can reduce unnecessary breast biopsies. Breast Cancer Research, published online Dec. 31, 2025. DOI: https://doi.org/10.1186/s13058-025-02206-3



Funding for this research was provided by the National Cancer Institute of the National Institutes of Health (R01CA228047).

Siteman Kids is the first site of multicenter CAR-T trial for autoimmune diseases

Access to the novel immunotherapy ­­— which “has the potential for cure” — is the latest offering by the national leader in pediatric hematology, oncology, and cell therapies.

Siteman Kids at St. Louis Children’s Hospital, along with WashU Medicine, is the first site to test a novel immunotherapy drug for the treatment of autoimmune diseases such as systemic lupus erythematosus, juvenile myasthenia gravis, juvenile dermatomyositis, and ANCA-associated vasculitis in children and young adults.

The clinical trial, called HELIOS Descartes-08 (202510129), evaluates dosing levels of an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets the B-cell maturation antigen (BCMA). Significantly, no neoadjuvant chemotherapy is needed prior to the start of Descartes-08 therapy.

“We are the first site in a multicenter clinical trial that will offer qualified patients an infusion of mRNA-modified CAR-T cells that target plasma cells,” said WashU Medicine hematologist/oncologist Melissa Mavers, MD, PhD, site principal investigator and a leader on the childhood cancers specialist team at Siteman Cancer Center. “This trial is exciting because this is the first available therapy targeting plasma cells in autoimmune disease and has the potential for cure for these patients.”

Earlier results of the Descartes-08 therapy, developed by Cartesian Therapeutics, have been promising. The FDA has granted it Orphan Drug Designation and Regenerative Medicine Advanced Therapy Designation.

To be eligible for the clinical trial, a patient must:

  • Be age 12 or older
  • Diagnosed with systemic lupus erythematous, juvenile myasthenia gravis, juvenile dermatomyositis, or ANCA-associated vasculitis
  • Have undergone systemic treatment

The trial will be administered through the Pediatric Hematopoietic Cell Transplant and Cellular Therapy Program at Siteman Kids at St. Louis Children’s Hospital.

Other Major Advancements

The clinical trial launch follows these recent advances at Siteman Kids:

Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (ALL/LBL)

The FDA granted Breakthrough Therapy Designation for WU-CART-007, an allogeneic CAR-T therapy for T-cell malignancies developed by WashU Medicine researchers at Siteman Cancer Center. WU-CART-007 is an off-the-shelf, anti-CD7 CAR T-cell therapy for children and adults diagnosed with relapsed or refractory T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma (R/R T-ALL/LBL). The FDA designation, announced in January, came after global clinical trials found that WU-CART-007 (also known as soficabtagene geleucel, or sofi-cel), resulted in 73% of adults and adolescents in the trials achieving full remission after receiving a full dose of the cellular therapy. WashU Medicine pediatric hematologist/oncologist Thomas Pfeiffer, MD, co-led the pediatric component of the clinical trial at Siteman Kids.

Learn more: U.S. FDA Grants to Wugen’s WU-CART-007 Breakthrough Therapy Designation

Brain Tumors

Global consultations and referrals continue to expand the reach and impact of an International Neuro-Oncology Tumor Board that originated at Siteman Kids. WashU Medicine neuro-oncologist Mohamed Shebl Abdelbaki, MD, director of the Pediatric Neuro-Oncology Program at Siteman Kids, began the monthly tumor board meetings in early 2021. To date, more than 2,500 health care specialists from 71 institutions in 41 countries have participated in the meetings, which have resulted in several advancements in best care practices for the management of complex brain tumors in infants, children and young adults.

Also available at Siteman Kids is participation in the CONNECT1906: PEP-CMV vaccine phase II clinical trial that is testing a CMV-directed peptide vaccine in children with recurrent medulloblastoma or newly diagnosed high-grade gliomas or diffuse intrinsic pontine gliomas. The multicenter study advances investigations into whether CMV-targeted vaccines can serve as a novel immunotherapeutic approach and boost responses against these cancers in pediatric patients. Eligible patients will receive a single, 5-day course of oral chemotherapy followed by PEP-CMV injections. Siteman Kids’ site principal investigator is Eric Thompson, MD.

For patients with malignant brain tumors, Siteman Kids also is involved in a multicenter phase I trial investigating the safety and dosing of intra-tumoral injections of NK cells in patients with recurrent or progressive tumors located in the upper part of the brain. Siteman Kids is one of only seven institutions offering this trial through the Pediatric Neuro-Oncology Consortium. WashU researchers are known internationally for their breakthroughs in the development and use of NK cell immunotherapies. Site principal investigators are WashU Medicine neuro-oncologists Mohamed Shebl Abdelbaki, MD, and Michael Angelo Huang, MD, MS.

“These are just a few of the leading-edge research efforts and collaborations we have underway at Siteman Kids,” said Jorge Di Paola, MD, chief of the Division of Pediatric Hematology and Oncology and the Elizabeth Finney McDonnell Endowed Chair in Pediatric Hematology Oncology at Siteman Kids at St. Louis Children’s Hospital and WashU Medicine. “We have 12 basic and translational research labs solely dedicated to advancing understanding and treatments for a wide range of pediatric cancers and more than 280 clinical trials available.”

For more information regarding clinical trials at Siteman Kids, email [email protected] or call 800-600-3606 to make a referral.

Learn about all active trials.

Inflammatory immune cells predict survival, relapse in multiple myeloma

New ‘atlas’ of immune cells in bone marrow cancer lays foundation for more reliable prognosis

A new study maps the immune cell landscape of bone marrow in patients with multiple myeloma, a rare cancer that develops in the plasma cells of the bone marrow and has no cure. This large immune cell atlas, which includes robust patient outcome data, provides unparalleled new insights into how the immune system interacts with cancerous plasma cells and can be used to determine how aggressive a patient’s multiple myeloma is likely to be. The knowledge may improve survival predictions, guide treatment decisions and help in the development of new immune-based therapies for patients with multiple myeloma.

The study — co-led by WashU Medicine researchers at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, in collaboration with the Multiple Myeloma Research Foundation (MMRF) and other leading institutions across the country — appears Jan. 9 in the journal Nature Cancer.

“It is time for a better understanding of the immune system in multiple myeloma,” said WashU Medicine co-senior author Li Ding, PhD, the David English Smith Professor of Medicine and a research member of Siteman. “In addition to targeting the cancerous plasma cells directly, we also want new and better ways to activate the immune system to attack the malignant cells. This large-scale immune cell atlas will serve as a critical resource to investigators studying multiple myeloma and working to develop better therapies.”

While considered a rare cancer, multiple myeloma is the second most common blood cancer after leukemia, accounting for about 15%-20% of new blood cancer diagnoses in the U.S. annually. Plasma cells are white blood cells in the bone marrow. When they grow out of control, they crowd out healthy blood cells. About 60% of patients are still living five years after diagnosis.

Many new treatment options have emerged for multiple myeloma in recent years that can extend survival for many patients, sometimes for more than a decade. Even so, the disease almost always returns after periods of remission, emphasizing the need for new and better options.

Several of the newest therapies for multiple myeloma are immune system-based, including CAR-T cells and what are known as bispecific antibodies. But researchers suspect there may yet be untapped opportunities for immune-based treatments for multiple myeloma, and the immune cell atlas is a new tool to harness in pursuit of such therapies.

“This immune atlas provides a roadmap for the next generation of myeloma care,” said coauthor and WashU Medicine oncologist Ravi Vij, MD, the Jeffrey S. and Prue H. Gershman Distinguished Professor of Medicine and a research member of Siteman. “As immunotherapies like CAR-T cells and bispecific antibodies become central to treatment, understanding the immune context in which they operate is essential. Clinically, this work lays the foundation for immune-informed risk stratification and rational development of new therapies that not only target the tumor but also restore effective anti-myeloma immunity.”

Vij treats patients with multiple myeloma and other blood cancers at The Blood Cancer Center at Siteman.

A cell-by-cell catalog of multiple myeloma

The research team performed a rigorous and cutting-edge genetic analysis called single-cell RNA sequencing of almost 1.4 million individual plasma and immune cells in bone marrow sampled from 337 newly diagnosed multiple myeloma patients. This type of analysis can reveal how individual immune cells may function — or become dysfunctional — in the context of multiple myeloma.

The data describe patients enrolled in MMRF’s CoMMpass Study, which is the first large-scale, long-running study of patients with multiple myeloma focused on analyzing disease progression and treatment response based on the genomic and molecular profiles of the patients. WashU Medicine is one of multiple sites participating in the CoMMpass Study.

The investigators found that patients with certain types of immune cells in their bone marrow at diagnosis were more likely than others to relapse quickly, meaning their cancer returned soon after a first round of treatment. The researchers identified signaling patterns between the cancer cells and immune cells that drive inflammation, which might be boosting the cancer’s growth in patients with aggressive disease.

The team also identified a type of T cell that had stopped working as expected and, rather than attacking the tumor as it should, acted to suppress immune activity against the cancer. Together, these findings could help make prognosis more accurate and aid in selecting the best therapies.

“This immune atlas represents the power of collaborative science,” said co-senior author and MMRF Chief Scientific Officer George Mulligan, PhD. “The MMRF’s CoMMpass Study, combined with the expertise from investigators at WashU Medicine and leading institutions across the country, has created an unprecedented resource that will accelerate discovery and improve outcomes for myeloma patients.”

Importantly, the researchers showed that knowledge of the immune environment in a patient’s bone marrow could improve upon current methods for predicting which patients are most likely to experience an aggressive course of the disease and have shortened survival. Such predictions can help guide treatment decisions in terms of matching the intensity of the treatment with the aggressiveness of the cancer.

Current methods for determining whether a patient has high-risk multiple myeloma versus standard risk rely on knowing the genetic features of the cancer cells combined with clinical aspects of the patient’s health. The new study found that adding an immune component to this analysis would likely improve the accuracy of the categorization.

“More work is needed to develop specific immune-based blood tests, for example, that clinicians could order to better identify the aggressiveness of a particular case of multiple myeloma and help them select the best treatments for that patient,” Ding said. “This immune cell atlas fills a gap in knowledge that is needed to develop these types of new clinical tools.”

The MMRF designed and funded this research, which involved collaboration among the Georgia Institute of Technology, Emory University, Harvard Medical School and the Icahn School of Medicine at Mount Sinai.

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Pilcher WC, Yao L, Gonzalez-Kozlova E, Pita-Juarez Y, Karagkouni D, Acharya CR, Michaud ME, Hamilton M, Nanda S, Song Y, Sato K, Wang JT, Satpathy S, Ma Y, Schulman J, D’Souza D, Jayasinghe RG, Ohlstrom D, Ferguson KE, Cheloni G, Bakhtiari M, Pabustan N, Nie K, Foltz JA, Saldarriaga I, Alaaeldin R, Lepisto E, Chen R, Fiala MA, Thomas BE, Cook A, Vieira Dos Santos J, Chiang I, Figueiredo I, Fortier J, Slade M, Oh ST, Rettig MP, Anderson E, Li Y, Dasari S, Strausbauch MA, Simon VA, Immune Atlas Consortium, Radkevich E, Rahman AH, Chen Z, Lagana A, DiPersio JF, Rosenblatt J, Kim-Schulze S, Lonial S, Kumar S, Bhasin SS, Kourelis T, Dhodapkar MV, Vij R, Avigan D, Cho HJ, Mulligan G, Ding L, Gnjatic S, Vlachos IS, Bhasin M. A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma. Nature Cancer. Jan. 9, 2026. DOI: 10.1038/s43018-025-01072-4.

This work was designed and supported by the Multiple Myeloma Research Foundation; the Myeloma Solutions Fund; the Paula C. and Rodger O. Riney Blood Cancer Research Fund; and the National Institutes of Health (NIH), grant numbers U24CA224319, U01DK124165, P30CA196521, R50CA211466, R35CA210084, 5K12CA090628, U24CA211006, U2CCA233303, PJ000021702, R01CA258776 and UL1TR004419. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Ratner receives $9.86 million grant to study cancers caused by retrovirus

Lee Ratner, MD, PhD, the Alan A. and Edith L. Wolff Professor of Oncology at WashU Medicine, has been awarded a five-year, $9.86 million grant from the National Institutes of Health (NIH) to investigate cancers caused by human retroviruses. This NIH Research Program Project Grant, which includes collaborators at The Ohio State University, supports a multidisciplinary effort aimed at solving a range of related problems focused on a central theme.

Led by Ratner, who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine, the projects are focused on developing ways to prevent and treat cancers caused by a virus called human T-cell leukemia virus type 1 (HTLV-1). When HTLV-1 infects the immune system’s T cells, they live longer than they should, letting genetic mutations build up that could lead the cells to become cancerous. This sometimes leads to a life-threatening blood cancer called adult T-cell leukemia or T-cell lymphoma.

With this new funding, Ratner and his colleagues will build on their studies of vaccines and how they could help prevent and treat HTLV-1 infections in an effort to stop the cancer from ever developing. With the goal of developing better therapies for patients with these cancers, the researchers are also investigating how infected T cells change their environment to ensure their own growth and survival. One example is Ratner’s work with Deborah Veis, MD, PhD, of WashU Medicine’s Division of Bone and Mineral Diseases, showing infected T cells produce small particles called extracellular vesicles that contribute to the destruction of bone tissue. Developing ways to counter such environmental changes could lead to new therapeutic strategies for patients.

Nasal drops fight brain tumors noninvasively

Nano-sized medicine boosts anti-cancer immune response, eradicates tumors in mice

Researchers at Washington University School of Medicine in St. Louis, along with collaborators at Northwestern University, have developed a noninvasive approach to treat one of the most aggressive and deadly brain cancers. Their technology uses precisely engineered structures assembled from nano-size materials to deliver potent tumor-fighting medicine to the brain through nasal drops. The novel delivery method is less invasive than similar treatments in development and was shown in mice to effectively treat glioblastoma by boosting the brain’s immune response.

The findings were published this month in PNAS.

Glioblastoma tumors form from brain cells called astrocytes and are the most common kind of brain cancer, affecting roughly three in 100,000 people in the U.S. Glioblastoma generally progresses very quickly and is almost always fatal. There are no curative treatments for the disease, in part because delivering medicines to the brain remains extremely challenging.

“We wanted to change this reality and develop a noninvasive treatment that activates the immune response to attack glioblastoma,” said Alexander H. Stegh, PhD, a professor and vice chair of research in the WashU Medicine Taylor Family Department of Neurosurgery and co-corresponding author of the study. Stegh also is research director of The Brain Tumor Center at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine. “With this research, we’ve shown that precisely engineered nanostructures, called spherical nucleic acids, can safely and effectively activate powerful immune pathways within the brain. This redefines how cancer immunotherapy can be achieved in otherwise difficult-to-access tumors.”

Cold Tumors Warmed with STING

Glioblastoma tumors are known as “cold tumors” because they do not induce the body’s natural immune response as do so-called “hot tumors” that are easier to treat with immunotherapies. Researchers have developed ways to spark an immune reaction against tumors by stimulating a pathway within cells called STING, which stands for stimulator of interferon genes. STING is triggered when a cell detects foreign DNA and activates the immune system to respond to the threat.

Past studies have shown that drugs activating STING in glioblastoma tumors can prime the body’s immune system to better fight the cancer. However, these agents break down quickly in the body and must be delivered directly into the tumor to work. Because repeated dosing is required for sustained benefit, relying on direct intratumoral administration requires highly invasive procedures.

“We really wanted to minimize patients having to go through that when they are already ill, and I thought that we could use the spherical nucleic acid platforms to deliver these drugs in a noninvasive way,” said Akanksha Mahajan, PhD, a postdoctoral research associate in Stegh’s lab and the first author on the study.

To overcome the problem, the Stegh team collaborated with co-corresponding author Chad A. Mirkin, PhD, director of the International Institute for Nanotechnology and the Rathmann Professor of Chemistry at Northwestern University, and his team. Mirkin invented spherical nucleic acids, a class of nanostructures that arrange DNA or RNA densely around a nanoparticle core, and he has shown that they have greater therapeutic potency compared to the standard delivery methods. The WashU Medicine and Northwestern researchers prepared a new class of spherical nucleic acids with gold cores studded with short snippets of DNA to trigger activation of the STING pathway in specific immune cells. To deliver these drugs to the brain, the team turned to the nose.

Intranasal therapy has been explored as a potential delivery method for medications targeting the brain, but no nanoscale therapies had yet been developed using this method to activate immune responses against brain cancers.

“This is the first time that it has been shown that we can increase immune cell activation in glioblastoma tumors when we deliver nanoscale therapeutics from the nose to the brain,” Mahajan said.

The team wanted to show that this approach could be used to deliver the medicine selectively to the brain, and that it would act on the appropriate cells once it got there.

For the first objective, they used a molecular tag on the spherical nucleic acid that was visible under near-infrared light. They found that the nanomedicine, when delivered as droplets into the nasal passages of mice with glioblastoma, traveled along the path of the main nerve that connects facial muscles to the brain. The immune response evoked in the brain by the medicine was concentrated in the specific immune cells, especially those in the tumor itself, and triggered some helpful responses in the lymph nodes. The medicine did not spread to other parts of the body where it might cause unwanted side effects.

Examinations of immune cells in and near the tumor showed that the therapy successfully activated the STING pathway and armed the immune system to fight the tumor.

When applied in combination with drugs designed to help activate T lymphocytes, another type of immune cell, the new therapy eradicated the tumors with just one or two doses and induced long-term immunity against their recurrence. Taken together, the results were much better than those of current STING-activating immune therapies.

Stegh cautioned that firing up the STING pathway isn’t capable of curing glioblastomas without reinforcement from other therapeutic approaches. Turning on the STING pathway by itself isn’t enough to fight glioblastoma, because the tumor has many ways to block or shut down the immune response that STING is meant to activate. His team is looking to add capabilities to their nanostructure that activate other immune responses. This could allow physicians to double or triple the therapeutic targets all in a single therapy.

“This is an approach that offers hope for safer, more effective treatments for glioblastoma and potentially other immune treatment-resistant cancers, and it marks a critical step toward clinical application,” said Stegh.

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Mahajan AS, Dussold C, Kim, S, Jarvis R, Hurley LA, Tommasini-Ghelfi S, Park J, Forsyth CM, Zhang B, Miska J, Heimberger AB, Mirkin CA, Stegh AH. cGAS-agonistic spherical nucleic acids reprogram the glioblastoma immune microenvironment and promote antitumor immunity. PNAS. Nov. 4, 2025. DOI: 10.1073/pnas.2409557122

This work was supported by the National Cancer Institute of the NIH (grant numbers P50CA221747 and R01CA275430), the NIH (grants R01CA120813, R01NS120547, and R01CA272639), the Melanoma Research Foundation, the Chicago Cancer Baseball Charities at the Lurie Cancer Center of Northwestern University and grants from Cellularity, Alnylam, and AbbVie. Imaging at Siteman Cancer Center Small Animal Cancer Imaging was supported by NIH instrumentation grants S10OD027042, S10OD025264, and National Cancer Institute Cancer Center grant P30CA091842. PET and MRI imaging was supported by Robert H. Lurie Comprehensive Cancer Center Grant P30CA060553.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Competing interests: Alexander Stegh is a shareholder of Exicure Inc., which develops SNA therapeutic platforms. Mirkin is a shareholder in Flashpoint, which develops SNA-based therapeutics. Stegh and Mirkin are co-inventors on patent US20150031745A1, which describes SNA nanoconjugates to cross the blood-brain barrier.