T-Cell Tolerant Fraction Can Predict Immunotherapy Toxicity

Cancer patients with clinically significant immune-related adverse events had significantly lower tolerant fraction
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Medically Reviewed By:
Mark Arredondo, M.D.

MONDAY, Aug. 21, 2023 (HealthDay News) -- 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

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