Effect of lactic acid concentration in microenvironment of cervical cancer on PD-L1 on the surface of cervical cancer cell in fractionated radiotherapy

Objective: To explore the correlation between lactic acid level and PD-L1 expression of cervical cancer cells in the microenvironment, and to analyze the impact of radiotherapy on PD-L1 expression of cervical cancer cells. Methods: The study is divided into two parts. Firstly, the radiotherapy-resistant Siha cell line was established by the method of multiple fractionation irradiation, and compared to the survival rate with the ordinary medium and the cells in the medium with different concentration of lactic acid following high dose irradiation. The Siha cells were cultured in ordinary medium and medium containing different concentrations of lactic acid, and the expression of PD-L1 was identified by Western blot after the cells were irradiated with small doses of multiple fractions. Secondly, 50 clinical samples were selected, the lactic acid concentration was identified by lactic acid kit, and the PD-L1 expression were identified by immunohistochemical before and after radiotherapy of 9Gy and 18Gy. Results: The expression of PD-L1 in cervical cancer tissues will change with the increase of the irradiation dose. Results indicated that the incidence of increased PD-L1 in patients with low PD-L1 expression during radiotherapy was considerably higher than that in patients with high PD-L1 expression. In cervical cancer tissue samples, we found that patients with high lactate concentration in cervical cancer tissues were more likely to have distant lymph node metastasis, and higher expression of PD-L1. Conclusions: Radiation therapy and Lactic acid in the tumor microenvironment can alter the PD-L1 expression in tumor cells, making them more resistant to radiotherapy. For patients with locally advanced, metastasis or recurrent cervical cancer, our research hints that the immune checkpoint inhibitors should be administrated at the early stage of radiotherapy for this combination treatment regimen.