Skip to main content

T-Cell Tolerant Fraction Can Predict Immunotherapy Toxicity

Medically reviewed by Drugs.com.

By Elana Gotkine HealthDay Reporter

MONDAY, Aug. 21, 2023 -- The T-cell tolerant fraction predicts clinically significant immune-related adverse events (irAEs) among patients with cancer treated with immune checkpoint inhibitors (ICIs), according to a study published in the August issue of the Journal for ImmunoTherapy of Cancer.

Jared Ostmeyer, Ph.D., from the University of Texas Southwestern Medical Center in Dallas, and colleagues examined T-cell receptor beta (TRB) locus sequencing from baseline pretreatment samples in 77 patients with cancer from an institutional registry (22 patients) and published studies (55 patients) receiving ICI therapy. TRB sequences for each patient were used to calculate the T-cell tolerant fraction, which was then examined as a predictor of future irAEs. The tolerant fraction was compared to TRB clonality and diversity.

The researchers found that cases with clinically significant irAEs had a significantly lower tolerant fraction and had an area under the receiver operating characteristic curve (AUC) of 0.79. From each ICI treatment category, the tolerant fraction was lower, reaching statistical significance for CTLA4. For T cells enriched against napsin A, a potential autoantigen of irAEs, the tolerant fraction was lower than other samples. In addition, thymic versus peripheral blood samples had a lower tolerant fraction, and the fraction was lower in some but not other autoimmune diseases (multiple sclerosis and type 1 diabetes, respectively). For predicting irAEs, TRB clonality and TRB diversity had AUCs of 0.62 and 0.60, respectively.

"In contrast to dynamic T cell clonal expansion or diversification, the tolerant fraction may be determined prior to ICI initiation, thereby potentially informing up-front selection of patients, treatments, and monitoring," the authors write.

One author disclosed ties to Amgen; several authors reported a U.S. patent application.

Abstract/Full Text

Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions.

© 2024 HealthDay. All rights reserved.

Read this next

Men Face More Diabetes Complications Than Women

FRIDAY, May 17, 2024 -- Men with diabetes have a greater risk for complications than women, irrespective of diabetes duration, according to a study published online May 16 in...

Diabetes Increases Risk for Functional Limitations in Older Adults

FRIDAY, May 3, 2024 -- Older adults with diabetes are more likely to develop functional limitations than adults without diabetes, according to a study published online April 16 in...

High-Efficacy Therapy Cuts Disability Progression in Pediatric MS

FRIDAY, April 12, 2024 -- Treatment of pediatric-onset relapsing-remitting multiple sclerosis with high-efficacy therapy reduces the risk for transition across disability states...

More news resources

Subscribe to our newsletter

Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.