Circulating CD137+ CD8+ T cells accumulate along with increased functional regulatory T cells and thoracic tumour burden in lung cancer patients.

Abstract

CD137 is a promising target for immunostimulation strategies against cancer. Previous studies showed that CD137+ CD8+ T cells are enriched in antitumour effector T cells in both preclinical tumour models and cancer patients, but to date, such T cells in the blood of lung cancer patients have not been sufficiently investigated. In this study, circulating antigen-activated CD8+ T cell subsets, identified as CD137+ CD8+ or PD-1+ (programmed cell death protein 1) CD8+ , and regulatory T cells (Treg), identified as CD4+ CD25+ CD127low/- , in 40 untreated lung cancer patients and in 49 age- and sex-matched healthy controls (HCs) were assessed by flow cytometry. Results were evaluated for associations with lung cancer patient clinical characteristics. Correlations between antigen-activated CD8+ T cells and effector Treg (CTLA-4+ [cytotoxic T-lymphocyte antigen 4] CD4+ CD25+ CD127low/- ) were also investigated. Higher percentages of PD-1+ , CD137+ and PD-1+ CD137+ amongst CD8+ T cells were observed in lung cancer patients compared with HCs. The percentages of CD137+ CD8+ and PD-1+ CD137+ CD8+ T cell subsets amongst CD8+ T cells were positively correlated with thoracic tumour burden and were strongly positively correlated with the percentage of effector Treg subset. Smoking patients harboured higher percentages of the PD-1+ CD8+ T cell subset compared with non-smoking patients. This study demonstrated that circulating antigen-activated CD8+ T cells accumulated in lung cancer patients along with increased effector Treg and thoracic tumour burden. These findings aid a better understanding of immune-host interactions in lung cancer patients using peripheral blood, and further support immunotherapeutic intervention strategies using combination therapy for differential control of Treg and activation of tumour-specific effector T cells.