Promotion of apoptosis of CD4+ T and CD8+ T lymphocytes induced by aberrant expression of programmed death ligand-1 in human cervical carcinomas

Abstract:

Objective：To investigate the expression of programmed death ligand-1（PD-L1） in human cervical carcinoma and the association between PD-L1 expression and T cell infiltration and to observe the effect of PD-L1 on apoptosis of active peripheral blood T lymphocytes of patients with cervical cancer in vitro. Methods：PD-L1 and programmed death receptor-1（PD-1） in human cervical carcinoma expressions were determined in 10 cases of normal cervical tissues and 67 cases of cervical carcinoma tissues by immunohistochemistry staining；the apoptosis of tumor infiltrating lymphocytes was examined by TUNEL assay；the number of tumor infil－trating CD4+ T and CD8+ T lymphocytes was determined by immunofluorescent staining and the apoptotic promoting effect of recombi－nant human PD-L1 protein on peripheral blood CD4+ T and CD8+ T lymphocytes was analyzed by flow cytometry. Results：No expression of PD-L1 in normal cervical epithelium was observed but expression of PD-L1 was found in 70%（47/67）cervical cancer tissues. PD-1 expression was found in part of tumor infiltrating lymphocytes. Some tumor infiltrating lymphocytes showed apoptosis. The tumor infiltrating CD8+ T cells were significantly reduced in PD-L1 positive cervical carcinoma cases（P＜0.05）. In vitro，recombinant hu－man PD-L1 induced apoptosis of activated peripheral blood T lymphocytes of healthy people and cervical cancer patients and the T cell apoptotic rates were significantly higher than those in blank group，which were （32.8±1.4）%，（38.3±1.5）%（P＜0.05） and （27.7±1.3）%，（30.9±1.9）%（P＜0.05）respectively. Anti-PD-1 antibody depressed PD-L1 induced T cells apoptosis，the apoptotic rates were （29.8±1.6）% and （31.6±1.4）%（P >0.05）. PD-L1 induced apoptosis of peripheral blood CD8+ T and CD4+ T cells. Con－clusions：PD-L1 is aberrantly expressed in cervical cancer. The expression of PD-L1 associates with lymphocytic apoptosis and de－crease of tumor infiltrating CD8+ T cells. PD-L1 promotes apoptosis of activated CD4+ T and CD8+ T cells by PD-L1/PD-1 pathway.