PDCD1 and neoplasm: In addition, lower expression of PD-L1 and TIM3 has been shown to be required for the strong anti-tumor effect of the combination, but TIM3 is a known marker of CTL exhaustion [32] and PD-L1 is a known ligand of PD-1 on CTLs [33], suggesting that a lower degree of CTL exhaustion is required for the strong anti-tumor effect of the combination treatment.