Expression And Clinical Significance Of PD-L1 In Cervical Cancer

Backgrade:Recent years,with the change of social lifestyle,the number of human papillomavirus(HPV)infections has increased,and the incidence of cervical cancer has increased significantly.Its morbidity and mortality rank among the female malignant tumors in China.4 digits.The incidence and mortality of cervical cancer in China is even higher than that of developed countries in North America.The most important treatment for gynecologic malignancies at this stage is surgical treatment,supplemented by radiotherapy and chemotherapy to reduce the recurrence rate and improve survival rate.However,traditional treatment methods still have problems such as large trauma and poor specificity.New tumor treatment methods need to be discovered and applied to clinical applications.In the process of occurrence and development of tumors,tumors can often escape and even inhibit the body's immune system to recognize and kill them.The immune system of the body to fight against tumor cells has not been able to make breakthrough progress,but with the tumor microenvironment and tumors.In-depth understanding of the immune escape mechanism,scholars have found that by suppressing the relevant signaling pathways that mediate tumor immune escape,tumor immune escape can be greatly reversed.Programmed death receptor 1(PD-1)/programmed death factor ligand 1(PD-L1)signaling pathway has been attracting attention as one of the important pathways that mediate tumor immune escape.PD-LI is a molecule of the B7 superfamily of costimulatory molecules,which is mainly expressed in antigen-presenting cells,activated T lymphocytes and B lymphocytes,inflammatory cells and malignant tumors,and has a function of inhibiting the activation of T lymphocytes.PD-L1,by binding to its receptor PD1,can provide negative regulatory signals,inhibit T cell activation and proliferation,promote T cell apoptosis,and cause tumor immune escape.It has been found that PD-L1 is highly expressed in malignant tumors such as lung cancer,liver cancer,breast cancer and cervical cancer.Once the expression of PD-L1 is up-regulated in tumor cells,it can increase the metastasis and invasion of tumor foci,and enable tumor cells to escape the attack of CD8+ T cells.Therefore,PD-L1 not only participates in the development of tumors,but also plays an important role in the immune escape of tumors.Currently,two types of immunotherapy approved by the FDA for clinical use are:(1)PD-1/PD-L1 antibodies;(2)cytotoxic T-cell lymphocyteassociated inhibitor protein 4(CTLA-4)antibodies.At present,antibodies targeting PD-1 or PD-L1 have been applied to a variety of malignant tumors,including melanoma,NSCLC,renal cell carcinoma,bladder cancer,colorectal cancer and gastric cancer,and the objective response rate is 16% to 100.%,tumor tissue PD-L1 expression can be used as an indicator of the efficacy of monoclonal antibodies.This experiment provides a valuable reference for the immunotherapy of cervical cancer by detecting the expression of PD-L1 in cervical cancer tissues.Objective:The study was aimed to examine the expression levels of PDL1 in normal cervical tissue,CIN and cervical cancer tisues,to envaluate the relationship between PD-L1 expression and clinicopathological parameters of patientswith cervical cancer and therefore to provide theoretical and experimental basis for immunotherapy of cervical cancer.Methods:1.PD-L1 protein expression level was determined in 10 cases of normal cervical tissue,71 cases of CIN tissues and 89 cases of cervical cancer tissues by immunohistochemical staining.The relationship between PD-L1 expression level and clinical pathological parameters of patients with cervical cancer was then envaluated using ?2 test.2.Ten cervical exfoliated cell lavage fluids from women with no HPV infection and 38 high-risk HPV infections were collected and sPD-L1 in the lavage fluid was rapidly determined ELISA.Results : 1.PDL1 is absent in normal cervical tissues,and expressed in both CIN and cervical cancer tissues,with positive rates of 42%(30/71)and 74%(66/89),respectively.CIN tissues showed weak PD-L1 immunostaining while cancerous tissues showed strong staining.The PD-L1 expression was higher in CIN tissues then in cervical cancer tissues.The expression of PD-L1 was not correlated with age,pathological grade and lymphatic metastasis of patients with cervical cancer(P>0.05),but was positively related with clinical stage(P=0.0021);2.Women with high-risk HPV infection often have higher sPD-L1 expression.Conclusions :1.PD-L1 has a gradual upward trend in the process of cervical carcinogenesis,indicating that it plays an important role in the immunosuppression of cervical cancer.2.By using ELISA,rapid detection of sPD-L1 in cervical exfoliated cell lavage fluid may assist clinicians in better assessing HPV infection status and even predict clinical outcomes.