Kakavand H, et al. – The potential mechanisms of acquired resistance to anti–PD–1 were scrutinized in this trial, in longitudinally collected metastatic melanoma patient biopsies. The results observed that negative immune checkpoint regulation by VISTA represented a significant potential mechanism of acquired resistance in the study cohort. Downregulation of HLA–associated antigen presentation occurred with acquired resistance. Augmentation of the VISTA immune checkpoint pathway displayed as a promising therapeutic strategy in metastatic melanoma patients, especially those failing anti–PD–1 therapy. It necessitated additional research.