Spatial distribution of PD-1+CD39+CD8+ T cell in TME refined its tumorigenic and immunotherapeutic biomarker in lung cancer

Abstract

Abstract Purpose CD8 + T cells in tumors are heterogenous and comprise multiple differentiation states. It has been reported that human tumor-infiltrating CD8 + T cells can express CD39 and more evidences proposed CD39 as a marker of exhausted and tumor reactive CD8 + T cells. However, no studies have delved into the spatial distribution of the CD39 + CD8 + T cell subsets in lung cancer, which could help to evaluate the immune microenvironment for developing the future immunotherapy approaches. Methods A total of 53 lung cancer patients prior to any therapy were included. A subset of tumor-infiltrating CD8 + T cells marked by expression of the immunosuppressive ATP ecto-nucleotidase CD39 and PD-1 was analyzed. Neoplasm-superficial biopsy and intratumoral EBUS-TBNA were used to assess the peripheral and central tumor microenvironment respectively. Results The CD39 + CD8 + T cells were ubiquitously infiltrated in lung cancer tissue, as well as dominantly accumulated in peritumoral compartment of larger tumor. In comparison to their CD39- counterparts, CD39 + CD8 + T cells from both sites showed significantly higher expression of PD-1 in line with co-distribution of PD-1 + CD8 + T cell in TME of lung cancer. Particularly, most of CD39 + CD8 + T cells located at peripheral TME exhibited an exhausted phenotype compatible with PD-1 expression in contrast to the reported center of tumor. Furthermore, compared with CD39 + CD8 + T cells, PD-1 + CD39 + CD8 + T cells act as a better biomarker to predict response to anti-PD-1 therapy. Conclusion Spatial heterogeneity may be critical to elicit CD39 expression on lung cancer associated CD8 + T cells. More increased of PD-1 + CD39 + CD8 + T cells within peripheral TME constitute tumorigenic role and act as a candidate biomarker for immunotherapy to lung cancer.