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Cervical cancer is one of the most common gynecologic malignant tumors that threaten the health of women. Recently some researches have found that radiotherapy combined with anti-PD-1/PD-L1 drugs might improve anti-tumor efficacy. But there is few report about this issue on cervical cancer field. In order to testify the possibility and feasibility in cervical cancer patients, we collected 70 tissue samples of cervical squamous cell carcinoma and 70 tissue samples of cervical benign lesion, of which 24 cases of the cervical squamous cell carcinoma had matched peripheral blood samples, compared to 30 cases with matched peripheral blood samples of benign lesions. We used immunohistochemistry to detect the expression of PD-L1 in the tissues and flow cytometry to detect the proportion of CD4+PD-1+ and CD8+PD-1+ subsets in peripheral blood. Then Log-rank and COX regression were used to analyze the relationship among survival time, expression of PD-L1 and proportion of PD-1+ T cells. The results indicated that the proportion of CD4+PD-1+ T cells and CD8+PD-1+ T cells in peripheral blood positively correlated with the expression of PD-L1 in tissue samples of cervical squamous cell carcinoma patients (R2=0.734, P=0.000; R2=0.66, P=0.000), while there were less correlation in cervical benign patients (R2=0.138, P=0.043; R2=0.174, P=0.022). There were significantly differences in the proportion of CD8+PD-1+T cells and PD-L1+ tissue cells between cervical cancer group and cervical benign disease group (P=0.000, P=0.002). With the increase of tumor stage, the percentage of CD4+PD-1+ T cells and CD8+PD-1+ T cells increased correspondingly. With the increase of tumor diameter and stage, the expression of PD-L1 in tumor tissue also increased. The patients with small proportion of CD4+PD-1+ T cells and low expression of PD-L1 seemed to have longer survival time. Multivariate analysis showed that the PFS time was affected by the expression of PD-L1(B=1.844, P=0.019). Taken together, the cervical squamous cell cancer patients had more CD4+PD-1+ T cells in peripheral blood and PD-L1+ cells in tissues, which correlated to the grading of tumor and associated with prognosis. Note: This abstract was not presented at the meeting. Citation Format: Yongxing Bao, Songan Zhang, Huerdidan Niyazi, Gulixian Tuluwengjiang, Lei Zhang, Yang Zhang, Weipeng Su. The expression level and prognostic value of PD-L1 and PD-1 in cervical carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-057. doi:10.1158/1538-7445.AM2017-LB-057

This study aimed to investigate the effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 signaling pathway. A total of 43 adult female Wistar rats were selected and injected with HeLa cells in the caudal vein to construct a rat model of cervical cancer. All model rats were randomly divided into the radiotherapy group ( n = 31) and the control group ( n = 12). The immunophenotype of Treg cells was detected by the flow cytometry. The protein expressions of EBI3, PD-1, and PD-L1 in cervical cancer tissues were tested by the streptavidin–peroxidase method. HeLa cells in the logarithmic growth phase were divided into four groups: the blank, the negative control group, the EBI3 mimics group, and the EBI3 inhibitors group. Western blotting was used to detect PD-1 and PD-L1 protein expressions. MTT assay was performed to measure the proliferation of Treg cells. Flow cytometry was used to detect cell cycle and apoptosis, and CD4+/CD8+ T cell ratio in each group. Compared with before and 1 week after radiotherapy, the percentages of CD4+T cells and CD8+T cells were significantly decreased in the radiotherapy group at 1 month after radiotherapy. Furthermore, down-regulation of EBI3 and up-regulation of PD-1 and PD-L1 were observed in cervical cancer tissues at 1 month after radiotherapy. In comparison to the blank and negative control groups, increased expression of EBI3 and decreased expressions of PD-1 and PD-L1 were found in the EBI3 mimics group. However, the EBI3 inhibitors group had a lower expression of EBI3 and higher expressions of PD-1 and PD-L1 than those in the blank and negative control groups. The EBI3 mimics group showed an increase in the optical density value (0.43 ± 0.05), while a decrease in the optical density value (0.31 ± 0.02) was found in the EBI3 inhibitors group. Moreover, compared with the blank and negative control groups, the apoptosis rates of Treg/CD4+T/CD8+T cells were decreased in the EBI3 mimics group, but the EBI3 inhibitors group exhibited an increase in apoptosis rate. In conclusion, over-expression of EBI3 could reduce the apoptosis of Treg/CD4+T/CD8+T cells and prevent radiation-induced immunosuppression of cervical cancer HeLa cells by inhibiting the activation of PD-1/PD-L1 signaling pathway.