Double PD-1 and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) expression in tumor-infiltrating lymphocytes from tumor-bearing mice identifies the most dysfunctional CD8+ T cells in the TME of these mice, and concurrent PD-1 and TIM-3 blockade significantly improves the antitumor activity of these cells, much better than single inhibition (63). The gene discussed is HAVCR2; the disease is neoplasm.