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‑γ 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.