CD8~+ T Cells Form The Predominant Subset Of NKG2A~+ Cells In Human Lung Cancer

Background: NKG2 A is an inhibitory receptor of both T cells and natural killer(NK)cells.Persistent activation promotes T cells and NK cells to express NKG2 A and results in the progression of chronic infection and cancer.However,the characteristics and subsets of NKG2A~+ lymphocytes in human lung cancer are still unclear.Methods: Here,we used the Tumor Immune Estimation Resource(TIMER)database and immune profiling of paired biospecimens to uncover the correlation between NKG2 A expression and immune infiltration levels in human cancer as well as the characteristics of NKG2A~+ lymphocytes in human lung cancer.Results: We found that KLRC1 expression was especially correlated with CD8~+ T cell infiltration levels in 34 types of human cancer through the TIMER database.Moreover,NKG2A~+ CD8~+ T cells were the predominant subset of NKG2A~+ lymphocytes in human lung cancer.In contrast,the NKG2A~+ NK cells were decreased in tumors compared with the paired normal lung tissue.Tumor-infiltrating NKG2A~+ CD8~+ T cells expressed tissue-resident memory T cell(TRM cell)and exhausted T cell markers.Cytokines and cytotoxic molecules secreted by tumor-infiltrating NKG2A~+ CD8~+ T cells were significantly lower than those secreted by NKG2A-CD8~+ T cells in vitro.When stimulated with T cell receptor(TCR)activator,tumor-infiltrating NKG2A~+CD8~+ T cells could secrete large amounts of granzyme B.Conclusions: Our findings demonstrate that tumor-infiltrating NKG2A~+ CD8~+ T cells form the predominant subset of NKG2A~+ cells in human lung cancer and suggest that targeting NKG2A~+ CD8~+ T cells is a promising approach for future anti-lung cancerimmunotherapy.