An Investigation Of PD-L1 Expression And Its Association With Tumor Infiltrating T Cells In Human Cervical Carcinomas

The low level of immunity in cervical microenvironment is an important factor in the genesis and progress of cervical cancer, Tumor infiltrating CD8+T is an independent prognostic factor in cervical cancer. The activation of T cells require the message from tumor antigen which presented by MHC molecules, and co-stimulating factor molecules, such as positive co-stimulating factor CD28 and negative co-stimulating factor programmed death ligand1. It was reported that multiple malignant tumors express PD-L1, which can combine with PD-1 of activated T cell, suppressed the proliferation and differentiation of T cells, and induced apoptosis of T cells.In this paper, PD-L1 and PD-1 expression was respectively determined in five cases of normal cervical tissue, 7 cases of high-level cervical intraepithelial neoplasia (CINⅡ-Ⅲ) and 67 cases of cervical carcinomas of human by immunohistochemistry staining; the tumor infiltrating CD4+T and CD8+T cell were determined by immunofluorescent staining, and the apoptosis of tumor-infiltration lymphocytes was examined by TUNEL assay in those cases.The results showed that no PD-L1 expressed in normal cervical epithelium; PD-L1 negatively or weakly expressed in epithelia of high grade CIN, the average relative optical density was (0.82±0.75); and PD-L1 expressed in 70% (47/67) cervical carcinomas, the average relative optical density in superficial infiltrating (<5mm) and deep infiltrating cervical squamous cell carcinomas was (2.70±1.68) and (2.90±1.72). PD-1 expressed in partial tumor-infiltrating lymphocytes in those cases. There was a significantly different PD-L1 expression between the epithelium of CIN and the cervical carcinomas (P < 0.01), PD-L1 expression density of superficial invasive cervical carcinomas was slightly lower than that of deep invasive cervical carcinomas, but there was no significant statistic difference between them. PD-L1 expression negatively associated with the number of tumor-infiltrating CD8+T cells (r =-0.82, P<0.01), but did not associate with the number of tumor-infiltrating CD4+T cells (r =-0.05, P> 0.05); cervical carcinoma cells in metastatic lymph node did not express PD-L1 although primary cervical carcinoma cells express PD-L1; apoptosis occurred in partial tumor-infiltrating lymphocytes in cervical carcinomas.The study concludes that cervical carcinoma cells express PD-L1, and PD-L1 expression negatively associates with the number of tumor-infiltrating CD8+T cells, but do not associates with the number of tumor-infiltrating CD4+T cells. Lymph node metastatic cervical carcinoma cells dose not express PD-L1 although primary cervical carcinoma cells express PD-L1. PD-L1/PD-1 pathway may play role on apoptosis of tumor-infiltrating lymphocytes.