Our findings therefore suggest that pemetrexed may exert a dual role in facilitating ICB therapy; pemetrexed can induce ICD to activate APCs and trigger the tumor infiltration of CD4+ T helper cells, and also induce the expression of PD-L1 in tumor cells that boosts the effects of ICB on the activation of CD8+ cytotoxic T cells. Here, CD8A is linked to neoplasm.