Association Of Dynamic Changes Of Immune-Related Cytokines In Peripheral Blood In The Process Of Anti-PD-1 Antibody Treatment With Efficacy In Advanced Cancer

[Objective]Anti-PD-1 antibody has made breakthrough progress in the treatment of advanced c ancer.In the treatment of diseases such as melanoma,lung cancer,renal carcinoma,bla dder neoplasms and Hodgkin's lymphoma which are resistance to chemotherapy,anti PD-1 antibody has obtained a good efficacy ,and the side effects can be tolerated.Anti PD-1 antibody terminate the suppression of T cell activity by blocking the co mbination of PD-1 and its ligand PD-L1 (B7-H1) ,then promote T cells produce cyt okines and destroy tumor cells. Cytokines play an important role in tumor microenvi ronment and tumor development.Measure the change of cytokines during the immunoth erapy can help surveillance the development of tumor, evaluate the body's immune status ,expected to find a biomarker which can predict therapeutic effect and progno sis of immunotherapy.[Methods]A total of 33 patients with advanced tumor treated by anti PD-1 antibody(Nivolum ab/Pembrolizumab) from April 2016 to January 2017 in PLA general hospital were compared with those from 35 healthy donors All patients were treated with intrave nous infusion,method:Nivolumab 3mg/kg ,every 2 weeks; Pembrolizumab 2mg/kg,every 3 weeks.Detect the concentration of 27 kinds of cytokines in peripheral blood b efore every cycle.Peripheral blood samples were analyzed by Luminex (27-Plex) kit.Evaluate the therapeutic efficiency every 3 cycles.SPSS 17.0 software was used for statistical analysis. A P value less than 0.05 was defined as statistic ally significance.[Results]1.The serum level of IL-2?IL-7?Basic FGF? GM-CSF? PDGF-bb in healthy gr oup was significantly higher than patients with advanced tumor, and the pretreatmen t level of IL-5?IL-6?IL-8?IL-15?IP-10?MIP-1a?MIP-1b?TNF-a in patients w ith advanced tumor was significantly higher than the healthy group.2?The serum level of IL-10?IP-10 in patients treated with anti PD-1 antibody was significantly increased after progression.3?After one cycle of PD-1 treatment,the serum level of Eotaxin in (PR+SD) gr oup was significantly higher than PD group ;and after three cycles of PD-1 treatme nt,the serum level of IL-6?IL-8 in PD group was significantly higher than (PR+S D) group .4?Comprehensive analysis of variation trend of various cytokines in the process o f 3 cycles and 6 cycles respectively in PR+SD group and PD group,we found that cytokines such as IL-1b?IL-6?IL-8?IL-9?MIP-1a?MIP-1p was stable in PR+SD group ,but the fluctuating rangeis relatively great or increased significantly in P D group,cytokines such as IL-1ra?IL-2?IL-15 show the opposite trend,they incre ased significantly in PR+SD group,but stable in PD group.[Conclusions]The changes of several cytokines in peripheral blood in the process of PD-1 treatment may be associated with the short-term effects of PD-1 immunotherapy .For example,the elevated concentration of cytokines IL-Ira?IL-2?IL-15 may indicate a good clinical curative effect,while the elevated concentration of cytokines IL-1b?IL-6?IL-8?IL-9?MIP-1a? MIP-1? may indicate a poor therapeutic effects. But as our sample size is small,we regard it as a exploratory study.Prospective clinical studies with larger samples are needed to confirm the conclusion.