Heterogenous expression of PD-1 within the tumor microenvironment could also sustain resistance against PD-1/PD-L1 antibodies and could potentially be overcome by targeting alternative immune molecules such as T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), either in conjunction with or as an alternative to PD-1 blockade[78]. This evidence concerns the gene HAVCR2 and neoplasm.