期刊
MOLECULAR MEDICINE REPORTS
卷 15, 期 3, 页码 1063-1070出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2017.6102
关键词
cervical cancer; E7 oncoprotein; human papillomavirus 16; programmed death-ligand 1; soluble programmed death ligand 1
资金
- Major Research Plan of the Hubei Province Natural Science Foundation of China [2012FFA086]
- Hubei Province's Youth Science and Technology Innovation Team [T201203]
Cytotoxic T lymphocyte dysfunction is frequently associated with PD-L1/PD-1 pathway activation, and is a principal obstacle in cancer therapy. In the present study, the mechanisms underlying the human papillomavirus (HPV)-induced evasion of cervical cancer cells to the host immune system via the programmed death ligand 1/programmed death 1 (PD-L1/PD-1) signaling pathway was investigated. A significant increase in the expression of the HPV16E7 viral protein and PD-Ll in cervical tissues was observed when compared with normal cervical tissues. In addition, a positive correlation between HPV16E7 and PD -L1 expression was observed by immunohistochemical staining and reverse transcription-polymerase chain reaction. Overexpressing HPV16E7 oncoprotein in the epithelial carcinoma of PC3 cells increased the expression level of the PD -L1 protein and inhibited peripheral blood mononuclear cell (PBMC) proliferation and cytotoxic T lymphocyte (CTL) activity. Upon knockdown of HPV16E7 in HPV16-associated CaSki cervical cancer cells with a relevant siRNA, a reduction in PD -L1 protein expression was observed, as well as a significant increase in PBMC proliferation and CTL activity. A recombinant plasmid, MSCVPIG-soluble PD -1, was constructed and transfected into the CaSki cell line, and was co -cultured with PBMCs. PBMC proliferation and CTL activity were observed to increase significantly. In conclusion, the results presented in the current study suggest that overexpression of PD -L1, induced by HPV16E7, may be responsible for lymphocyte dysfunction. In addition, soluble PD -1 may restore the function of tumor -infiltrating lymphocytes by inhibiting the PD-Ll/PD-1 signaling pathway. These results may provide a novel insight for immunotherapeutic approaches in the treatment of cervical cancer.
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