Expression And Clinical Significance Of Programmed Death-1 On Lymphocytes And Programmed Death Ligand-1 On Monocytes In The Peripheral Blood Of Patients With Cervical Cancer

Cervical cancer is the most common gynecologic malignant tumor. Occurrence and progression of cervical cancer is closely related to immune system, in addition to various factors including viral or bacterial infection, birth trauma, stimulation of carcinogenic substances, sexual disorder and environment etc. Many factors are involved in the interaction of tumor tissue and immune system within the tumor microenvironment. PD-1/PD-L1 has attracted much attention in recent years. Recent research shows that the PD-L1, a member of negative co-stimulatory molecules, expresses in many cancer cells, cancer tissues and interacts with PD-1 on tumor-infiltrating lymphocytes (TIL), inhibiting activation of TIL and facilitating disease progression. Furthermore, levels of soluble PD-L1 were elevated in lung cancer and aggressive diffuse large B-Cell lymphoma, which acts as an antagonist, blocking PD-1/PD-L1 engagement and increasing the proliferation and cytokine production of T cells. However, the roles of PD-1/PD-L1 on circulating immune cells and sPD-L1 in cervical cancer remain unclear.We set to examine the expression of PD-1 on CD4+ and CD8+ T cells and PD-L1 on CD14+ monocytes in peripheral blood and the level of sPD-L1 in serum of cervical carcinoma patients, and to explore their clinical implications.[Objective] To investigate the expression and clinical significance of PD-1/PD-L1 on lymphocytes and CD14+monocytes in the peripheral blood and sPD-L1 in serum of patients with cervical cancer.[Methods] A total of 40 healthy controls (HC),40 CIN patients and 66 newly diagnosed cervical cancer patients were recruited from the Department of Obstetrics and Gynecology, the First Affiliated Hospital of Soochow University and the Second Affiliated Hospital of Soochow University. The complete date range for patient recruitment was from September 2014 to September 2015. Expression of PD-1 on peripheral CD4+T and CD8+ T cells and PD-L1 on monocytes was analyzed by flow cytometry. Level of soluble PD-L1 (sPD-L1) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Written informed consent was obtained from each subject or a legally authorized representative before blood sampling. The study was approved by the local Ethics Committee.[Results] There was no difference of circulating CD4+T, CD8+T cells and CD14+moncytes frequency among cervical cancer, CIN and HC. PD-1 expression on CD4+ and CD8+ T cells was significantly increased from HC to cancer, whereas PD-L1 expression on CD14+ monocytes was increased from HC to CIN but leveled off in cancer. Data revealed that PD-1 on CD4+T cells was positively correlated with PD-1 on CD8+T cells in cancer, however, no correlation was found between PD-1 and PD-L1 expression. Furthermore, expression of PD-1 on CD4+ and CD8+ T cells was positively correlated with FIGO stage. Level of sPD-L1 in cervical cancer patients, CIN patients and healthy controls were all in low level and there was no difference among them.[Conclusion] PD-1/PD-L1 pathway may be involved in the occurrence and progression of cervical cancer by its regulation on circulating immune cells. PD-1 on T cells and PD-L1 on CD14+ monocytes may be potent predicting biomarkers and may indicate usefulness of alternative immunological therapeutic strategies using PD-1 axis inhibitors for cervical cancer. However, sPD-L1 exists in serum of cervical carcinoma patients with low level, which can not be potent predicting biomarkers of cervical cancer.