A sobering "check" on immune checkpoint inhibitors

In this issue of Blood, Rauch et al analyze primary cells from human T-cell leukemia virus-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) patients treated on a phase 2 clinical trial with nivolumab to elucidate mechanisms of hyperprogression that halted the trial after just 3 patients received a single treatment.(1) Small numbers limit the report as only 2 of 3 patients provided consent for posttreatment sample collection, but the hypotheses generated contain important information for both a rare disease and an increasingly used cancer therapy. Notably, in ATLL, PD-1 blockade may function as a tumor suppressor, disrupt tolerogenic suppression, upregulate additional checkpoints, and/or cause ATLL cells to express growth factors.