Infiltrating T lymphocytes in the tumor microenvironment of small cell lung cancer: a state of knowledge review

Immune checkpoint inhibitors (ICIs) have brought new hope for the treatment of patients with small cell lung cancer (SCLC) over the past decades. However, the overall response rate is limited, and is lower than that in non-small cell lung cancer (NSCLC). This is in part because of the lack of pre-existing tumor-infiltrating T lymphocytes (TITLs), especially cytotoxic T cells (CTLs), in the SCLC tumor microenvironment (TME), resulting in insufficient anti-tumor immune response. To unleash the full potential of ICIs, the trafficking and infiltration of TITLs to the tumor is necessary and tightly regulated, the highly immunosuppressive tumor microenvironment blunts the infiltration and function of TITLs that reach the tumor in SCLC. Here, we review the characteristics of TITLs, the effects of various factors on T cell infiltration, and possible strategies to restore or promote T cell infiltration in the TME of SCLC.