Despite striking therapeutic benefits for some patients, cancer immunotherapy using checkpoint-blocking drugs can cause toxic and potentially fatal side effects, including inflammation of the skin, liver, and gastrointestinal tract.
Researchers attempted to determine whether such side effects stem from drug-induced unchecked T-cell activity against unintended cellular targets in blood. To retrospectively detect signs of T-cell expansion in peripheral blood, the authors sequenced T-cell receptor genes from helper and killer T cells in blood collected from 27 patients treated with the checkpoint blocker ipilimumab and androgen deprivation therapy (ADT) in a phase II trial of metastatic castration-sensitive prostate cancer that was prematurely terminated due to safety concerns.
Blood samples collected before the onset of toxic side effects in treated patients revealed a link between grade 2–3 adverse events and the expansion of 55 or more killer T-cell clones in blood, suggesting that such clonal expansion might contribute to checkpoint drug toxicity.
Separate analysis of a cohort of nine patients treated with ipilimumab and ADT for localized, castration-resistant prostate cancer confirmed the link. According to the authors, prospective, longitudinal studies of a large cohort of patients could help determine whether T-cell clonal expansion can serve as a clinically useful biomarker to identify patients at risk of developing toxic side effects from checkpoint-blocking cancer immunotherapy drugs.