Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8^(+ ) T lymphocytes in human non-small cell lung cancer

摘要

T-cell tolerance is an important mechanism for tumor escape,but the molecular pathways involved in T-cell tolerance remain poorly understood.It remains unknown whether the inhibitory immunoreceptor programmed death-1(PD-1)plays a role in conditions of human non-small cell lung cancer(NSCLC).In this study,we detected PD-1 expression on CD81 T cells from healthy control peripheral blood mononuclear cells(PBMCs)and the PBMCs of NSCLC patients as well as NSCLC tissues.Results showed that tumor-infiltrating CD81 T cells had increased PD-1 expression and impaired immune function,including reducing cytokine production capability and impairing capacity to proliferate.Blockade of the PD-1/PD-L1 pathway by the PD-L1-specific antibody partially restored cytokine production and cell proliferation.These data provide direct evidence that the PD-1/PD-L1 pathway is involved in CD81 T-cell dysfunction in NSCLC patients.Moreover,blocking this pathway provides a potential therapy target in lung cancer.