Relationship between expression of PD-L1 and PD-L2 on esophageal squamous cell carcinoma and the antitumor effects of CD8+ T cells

The programmed death-1 (PD-1)/programmed death-ligands (PD-Ls) signal pathway has been implicated as a potential immune escape mechanism in several human cancers. However, the studies of PD-1/PD-Ls pathway in esophageal squamous cell carcinoma (ECSS) are not yet sufficient. The current study investigated the expression of PD-L1, PD-L2 and PD-1 in ESCC tissues. The correlations between the expression of these proteins and clinical histopathological parameters were analyzed. Then the stable transfected Ec109 cell lines overexpressing PD-L1/PD-L2 were established by plasmid transfection successfully. Ec109 and CD8(+) T cells were co-cultured to analyze the effects of PD-1/PD-Ls signal pathway on the function of CD8(+) T cells including proliferation, apoptosis and interferon-gamma production. We found that PD-L1-positive patients had significantly poorer prognosis than the negative patients, while their prognosis was not related to PD-L2 expression. The count of PD-1(+) TILs (tumor-infiltrating lymphocytes) was negatively correlated with both PD-L1 and PD-L2 expression. In functional studies, we found that PD-1/PD-Ls signal pathway was able to downregulate the function of CD8(+) T lymphocyte and its function could be restored by blocking the signal pathway. This indicates that PD-1/PD-Ls may prevent effective antitumor immunity, which provides important evidence to delineate the cellular immune deficiency mechanism in ESCC. Therefore, PD-1/PD-Ls are predicted to become novel targets for ESCC immunotherapy.