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⁺ CD127^low/- , 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⁺ CD127^low/- ) 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.

Keywords: CD137 (4-1BB); PD-1 (CD279); T cells; Treg cells; lung cancer.