Relationship between changes in expression of GITR and OX40 on PBMCs with immunotherapy response in intermediate and advanced cancer

Objective To find out the relationship between clinical efficacy and changes in co-stimulatory immune biomarkers on peripheral blood monocular cells (PBMCs) in intermediate and advanced cancer patients undergoing anti PD-1 monoclonal antibody treatment. Methods Twenty-one patients diagnosed as intermediate and advanced cancer received nivolumab or pembrolizumab in Chinese PLA General Hospital from December 2016 to August 2017 were selected. Every patient received at least two cycles of treatment, and 5 ml venous blood was collected before each treatment. Flow cytometry analysis was used to test the expression of OX40 and GITR on T lymphocyte, and the relationship between their changes and clinical efficacy was analyzed. The treatment lasted for two cycles (21 day per cycle). After treatment, according to the RECIST1.1 standard, patients were divided into response group (n=16) and non-response group (n=5). The differences of expression of OX40 and GITR were compared between two groups. Results Of the 21 cases, there were 16 males and 5 females with mean age of 58 years (ranging from 39 to 81 years). Fifteen cases had lung cancer, 2 cases had esophageal cancer, 2 cases had cervical cancer and 2 cases had urethra tumor. After the second cycle of immunotherapy, the expressions of GITR on CD4⁺ lymphocyte, CD8⁺ T lymphocyte and NK cells in non-response group were significantly higher than those of response group (P=0.007, 0.007, 0.002, respectively), and the expression of OX40 on CD4⁺lymphocyte of non-response group was significantly higher than that of response group (P=0.039). Conclusion The expressions of co-stimulatory immune biomarkers on PBMCs has changed in intermediate and advanced cancer patients undergoing anti PD-1 monoclonal antibody treatment, and GITR in responsive patients is significantly different with that in nonresponsive patients, which may be an index to predict outcomes of immunotherapy.