TNF and non-small cell lung carcinoma: TILs, CD4+ and CD8+ T cells, can secrete antitumor cytokines such as IL-2, TNF-α and IFN-γ, while the effector activities for producing these cytokines could be extinguished due to T-cell exhaustion.30 31 Our data from the NSCLC/T cell coculture systems and syngeneic mouse models indicate that pemetrexed alone suppresses the ability of T cells to produce IL-2 and IFN-γ because of PD-L1 upregulation, while the levels of IL-2 and IFN-γ can be restored or even further enhanced in the combinational treatment of pemetrexed and anti-PD-1/PD-L1 antibodies.