Biomarkers linked to side effects from cancer immunotherapy
UTSW-led study finds immune signals in blood may help predict toxicities, marking a step toward safer, more personalized treatment
DALLAS – Sept. 16, 2025 – A team led by UT Southwestern Medical Center scientists has identified early signals from the immune system that could help predict which cancer patients are most likely to develop harmful side effects from immunotherapy. The findings, published in the Journal for ImmunoTherapy of Cancer, offer a path toward tests to help doctors tailor care for at-risk patients.
“Through a multi-omic biomarker analysis, we identified a pre-existing but clinically silent proinflammatory state in patients with increased risk of immunotherapy toxicities,” said David Gerber, M.D., Professor of Internal Medicine in the Division of Hematology and Oncology and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern. Dr. Gerber, who is also co-Director of the Office of Education and Training in the Harold C. Simmons Comprehensive Cancer Center, co-led the study with first author Shaheen Khan, Ph.D., who was previously Assistant Professor of Pathology at UT Southwestern.
Immune checkpoint inhibitors – drugs that enhance the immune system’s ability to attack cancer – have transformed treatment for many cancers and extended lives even in patients with advanced disease. But they can also spark reactions that damage healthy organs, sometimes causing serious and lasting complications. More than half of patients receiving immunotherapy experience side effects, which remain difficult to predict or diagnose.
By analyzing blood from 162 patients at UT Southwestern and Parkland Health before and after immunotherapy treatment, researchers identified three key features linked to higher risk: elevated levels of antibody-producing cells and autoantibodies, stronger activity from inflammatory molecules such as interferon-gamma, and heightened signals from another key inflammatory molecule known as tumor necrosis factor or TNF. Patients with these immune profiles were more likely to develop side effects once treatment began.
“If prospectively verified, these findings potentially impact patients with any cancer types that are treated with immunotherapy,” said study co-author Mitchell von Itzstein, M.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology at UT Southwestern. “Currently, immunotherapy is used to treat most cancers in advanced stages as well as some cancers in earlier stages.”
The study builds on more than a decade of work at the UT Southwestern Simmons Cancer Center, where Dr. Gerber and other researchers have developed an institutional registry of immunotherapy patients and biospecimens. With contributions from more than 800 patients cared for at UT Southwestern and Parkland Health, the registry has enabled one of the most comprehensive efforts to date to connect immune, genetic, and antibody changes with treatment complications.
While the results are promising, the authors noted further research is needed to confirm these biomarkers in larger and more diverse groups and translate them into tools for patient care.
“The prediction, diagnosis, treatment, and monitoring of immune-related side effects remain major clinical challenges,” said study co-author Jeffrey A. SoRelle, M.D., Assistant Professor of Pathology and Pediatrics and a member of the UTSW Immunology Graduate Program. “Identifying the molecular mechanisms behind these side effects may help predict which patients are at greatest risk and potentially provide guidance for the treatment of these toxicities.”
Dr. Gerber holds the David Bruton, Jr. Professorship in Clinical Cancer Research. Dr. von Itzstein is a member of the Simmons Cancer Center.
A full list of contributors and their disclosures can be found in the published study.
This study was funded by the National Institute of Allergy and Infectious Diseases (1U01AI156189-01 and K08AI155832), an American Cancer Society-Melanoma Research Alliance Team Award (MRAT-18-114-01-LIB), a V Foundation Robin Roberts Cancer Survivorship Award (DT2019-007), a Melanoma Research Alliance and Society for Immunotherapy of Cancer Young Investigator Award (619351), the University of Texas Lung Cancer Specialized Program of Research Excellence (SPORE) (P50CA070907-21), and a National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543).
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.
About Parkland Health
Parkland Health is one of the largest public hospital systems in the country. Premier services at the state-of-the-art Parkland Memorial Hospital include the Level I Rees-Jones Trauma Center, the only burn center in North Texas verified by the American Burn Association for adult and pediatric patients, and a Level III Neonatal Intensive Care Unit. The system also includes two on-campus outpatient clinics – the Ron J. Anderson, MD Clinic and the Moody Outpatient Center, as well as more than 30 community-based clinics and numerous outreach and education programs. By cultivating its diversity, inclusion, and health equity efforts, Parkland enriches the health and wellness of the communities it serves. For more information, visit parklandhealth.org.