The Characteristics of Naive-like T Cells in Tumor-infiltrating Lymphocytes from Human Lung Cancer

Adoptive cell therapy using autologous tumorinfiltrating lymphocytes (TILs) or genetically modified lymphocytes from TILs is a new effective approach, but the application of TIL immunotherapy is still limited in many solid tumors. Knowledge of the classification and function of TILs is important to develop personalized immunotherapy with TILs in non-small lung cancer (NSCLC). In this study, we show the characteristics of T-cell subsets in TILs isolated from NSCLC. CD3⁺ CD8⁺ CD45RA⁺ T cells outnumbered CD3⁺ CD4⁺ CD45RA⁺ T cells in CD45RA⁺ TILs, but it was the opposite in CD45RO⁺ TILs. Effector memory CD4+ T cells predominated in CD4⁺ TILs; about 10% of the stem cell-like memory T cells (Tscm) were detected in TILs. To further analyze their functions, we stimulated TILs from NSCLC patients by mitogens to examine cytokine production. Our data demonstrated that naive-phenotype T cells in TILs secret IFN-g in abundance; TNF-α-producing T cells were significantly increased in TILs; there were more IL-17-expressing CD4+ Tscm cells than other subtypes of CD4+T cells in TILs. Our findings indicate that the CD4⁺/CD8⁺ naive-phenotype T cells and Tscm cells in TILs from lung cancer exhibit distinct composition and strong cytokine production. Attributes of Tscm cells from a naive-like T-cell population in TILs are the promising cell type for adoptive cell therapy in human lung cancer.