Accumulation Of CCR7-CCL21 In Serous Ovarian Cancer Correlates With The Migration Of PD-1

Purpose: The occurrence of cancer is the progress of tumor microenvironment and the result of the interaction between the immune system,mainly divided into the following three stages: clear(the immune system inhibits the growth of tumor);Balance(the cytotoxic T cells causing the proliferation and death of tumor cells and then enter the state of immune balance);Escape(tumor microenvironment makes tumor cells evade immune surveillance and then develop into clinical tumor).In the tumor microenvironment,a wide variety of tumor cells and stromal cells can secrete chemokines and directly affect the migration of various immune cells.Studies have shown that high expression of PD-1 within tumors plays a negative role of the progress of cancer,nowadays the immunotherapy of tumor in clinical achieved a good development,but the effect is not stable,how to guarantee the effect of immunotherapy in ovarian cancer is our current problem.Comprehensive above factors,we committed to whether the chemokine receptor-ligand pair CCR7-CCL21 was associated with the migration of program death ligand 1+(PD-1+)cells and affects disease progression and immune suppression of High-Grade Serous Ovarian Cancer(HGSOC).Experimental Design: Flow cytometry was used to analyze the densities of CD45+CD3+ PD-1+CCR3+ T cells,CD45+CD3+ PD-1+CCR5+ T cells and CD45+CD3+ PD-1+CCR7+ T cells in peripheral blood and tumors from 27 patients with HGSOC and the matched group.Combined with the clinical data,we analyzed the relationship between the expression of chemokines and the progress of tumor.We used a vitro Transwell system to determine whether CCR7-CCL21 was associated with the migration of PD-1+ T cells,after that we examined the CCL19 and CCL21 levels of HGSOC patients' peripheral blood and tumor tissues by ELISA.Results: The expression of PD-1 and CCR7 in HGSOC patients were much higher than that in matched group.PD-1 expression was more frequent in tumor tissues than peripheral blood,while CCR7 expression was much higher in peripheral blood than tumor tissues.The percentage of CD45+CD3+PD-1+CCR7+T cells and the ratio of PD-1 to CCR7 in tumor tissues of HGSOC patients were much higher than that in peripheral blood.In addition,there were a high expression of CCL21 and CCL19 in the tumor microenvironment of HGSOC patients.The tumor microenvironment appears to attract more CD45+CD3+PD-1+CCR7+ lymphocytes from peripheral blood,which may accelerate disease progression.Conclusions: CCL21 in the tumor microenvironment may play an important role in the migration of CD45+CD3+PD-1+CCR7+ T cells from peripheral blood and then cause immune suppression of the tumor microenvironment.