Researchers have identified a novel parameter of T cells that may help oncologists anticipate which patients are most likely to develop immunotherapy toxicity. The findings, published by Ostmeyer in the Journal for ImmunoTherapy of Cancer, could lead to improved treatments for a variety of cancers.
Immunotherapy has grown rapidly in recent years as a treatment for a wide range of common cancers. Some patients, however, acquire immune-related adverse events, which can affect almost any organ system at any point during or after treatment. In rare cases, they can be fatal.
Study Rationale
“The ability to predict which patients may develop significant immunotherapy toxicity would be extremely useful in the selection of patients, treatments, and monitoring,” said senior study author David Gerber, MD, 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 (UTSW). “Our metric—which we call the ‘tolerant fraction’—could play a role in making that a reality.”
The tolerant fraction represents the proportion of T cells not expected to attack normal cells or tissues. To develop and test this parameter, UTSW researchers profiled the receptors of T cells in 77 patients treated with immunotherapy. They also used publicly available data from patients with autoimmune disease and 786 healthy subjects.
“When we compared the new metric to previously studied parameters, the tolerant fraction predicted future immunotherapy toxicity more accurately,” noted Dr. Gerber, who is also a member of UTSW’s Harold C. Simmons Comprehensive Cancer Center. “Patients with a higher percentage of tolerant T cells appear less likely to develop an immune-related adverse event.”
Looking Ahead
The team’s findings are preliminary and will need to be confirmed by larger prospective studies, but they hold promise for the development of a novel approach to prevent immune-related adverse events.
“Today, immunotherapy toxicities are entirely unpredictable, and there isn’t a clear standard for how to monitor patients for potential immune-related adverse events” Dr. Gerber added. “As a result, some clinicians may be reluctant to use immunotherapy for early-stage cancers or to recommend the most aggressive and potentially toxic treatments, such as combination immunotherapy regimens. The ability to understand a patient’s risk for these toxicities and customize clinical monitoring could lead to more patients receiving more effective treatments more safely.”
Disclosure: The study was funded in part by the National Institute of Allergy and Infectious Diseases, an American Cancer Society-Melanoma Research Alliance Team Award, a V Foundation Robin Roberts Cancer Survivorship Award, the University of Texas Lung Cancer Specialized Program of Research Excellence, a Mary Kay Ash International Fellowship, the University of Texas Stimulating Access to Research in Residency, and the Harold C. Simmons Comprehensive Cancer Center Data Science Shared Resource. For full disclosures of the study authors, visit jitc.bmj.com.
