Multiple biomarkers of response to anti-PD-(L)1 blockade across tumors have been described including CD8+ tumor-infiltrating lymphocytes (TIL),14-16 PD-L1 expression,15,17,18 tumor mutation burden (TMB),19-21 changes in exhausted-phenotype CD8+ T cells peripherally22,23 and CD8+ T-cell clonotypic expansion intra-tumorally and peripherally.24-26 However, developing a specific, cost-effective, reproducible, and clinically actionable biomarker to anti-PD-(L)1 blockade remains elusive. The gene discussed is CD8A; the disease is neoplasm.