CD103+CD8+ T lymphocytes in non-small cell lung cancer are phenotypically and functionally primed to respond to PD-1 blockade

CD103(+) CD8(+) tumor infiltrating lymphocytes (TILs) have been linked to prolonged survival in various types of cancer including non-small cell lung cancer (NSCLC). However, the factors associated with the retention of CD103(+) CD8(+) TILs in lung cancer tissues remain largely unknown. Additionally, the contribution of CD103(+) CD8(+) TILs to effective PD-1 based immunotherapy has not been fully elucidated. In this study, we identified that the expression levels of E-cadherin and TGF-beta were significantly correlated with the distribution and the density of CD103(+) TILs in lung cancer tumor tissues. Unexpectedly, we observed that CD103(+) CD8(+) TILs that expressed higher levels of PD-1 co-express Ki-67. Moreover, CD103(+) CD8(+) TILs expressed an increased level of T-bet compared to their counterparts, indicating these cells may be better armed for immunotherapy. Lastly, PD-1 pathway blockade led to a significantly increased production of IFN-gamma by CD103(+) CD8(+) TILs, suggesting CD103(+) CD8(+) TILs could serve as a predictive biomarker for PD-1 based immunotherapy.