HAVCR2 and cancer: In human cancers, TIM-3 expression indicates an exhausted immune phenotype and correlates with poor outcome.74–79 Blockade of TIM-3 plus PD-1 showed synergy in preclinical models.80,81 Representative TIM-3 blocking antibodies cobolimab, sabatolimab, and LY3321367 showed good safety but limited efficacy in combination with anti-PD-1 antibody in phase I trials82–84 (Table 1 and Supplementary Table 1).