In the context of chronic antigen exposure, T-cell depletion is an inevitable corollary, and the criteria for assessing the efficacy of ICIs therapy differ between periods of T-cell depletion: Evidence of CD8+ T-cell depletion in pre-treatment and early treatment tumor samples predicts a clinically benign outcome of ICI treatment; depletion markers observed late in treatment and post-treatment predict an unfavorable clinical outcome (67, 68). The gene discussed is CD8A; the disease is neoplasm.