Association Of Dynamic Changes Of Immune-ralated Cytokines In Peripheral Blood With Efficacy And Survival In Advanced Non-small Cell Lung Cancer

[Objective]In the past ten years, comprehensive treatment of non-small cell lung cancer has made a considerable progress. Selecting the appropriate treatment according to the molecular pattern and evaluation of predictive factors is significant in prolonging survivals and improving the quality of life. Cytokines belong to biological indicators. They play an important role in the regulation of cell growth, maturation, differentiation and tumor development. Observing the dynamic changes of immune-ralated cytokines in peripheral blood is conductive to evaluating the efficacy of treatment and predicting the prognosis of disease.[Methods]Patients with unresectable advanced NSCLC from Jul 2012 to Dec 2013 were recruited in our study. The protein level of seven cytokines (IL-2、IL-6、TGF-β、HIF-1α、 PD-1、PD-L1、CTLA-4) was examined by ELSA. We analyzed the relationship between cytokines and clinicopathological features of patients and observed the dynamic changes in peripheral blood during the treatment, expected to find the association with efficacy and prognosis. SPSS 17.0 software was used for statistical analysis. A P value less than 0.05 was defined as statistically significance.[Results]1.111 cases were enrolled for our study. Untill the last follow-up,97(87.4%) patients had experienced disease progression. The median PFS was 7.9 months.62(55.9%) patients had died.The median OS was 19.2 months. Smoking, EGFR gene status and TNM staging had effects on PFS. Smoking and TNM staging were independent prognostic factors of PFS. Pathological type, EGFR gene status, age and the type of treatment had effects on OS. The type of treatment was independent prognostic factor of OS. Patients with driver gene alterations and having the specific molecular targeted therapy had longer median OS than patients without driver gene alterations.2. The serum level of IL-6, TGF-(3 and CTLA-4 in patients with advanced NSCLC was significantly higher than the healthy group (P<0.01). Women had the higher TGF-P and PD-1 serum level than men. Patients in stage IV had the lower IL-6 level than patients in stage III. The serum level of IL-6 and PD1 in adenocarcinoma patients was higher than those with mixed pathological type. Patients with well differentiation had the higher level of IL-2, IL-6, TGF-β, HIF-1α, PD-1, PDL-1, CTLA-4 than those with poorly differentiation.3. The immune status was changed once in the PR and PD group during the chemotherapy, while the SD group changed twice. The change occurred after the first cycle chemotherapy in PR group and after the second cycle in PD group. No significant changes of the seven cytokines were observed after two cycles of chemotherapy in PR group (P>0.05). The serum level of TGF-P, PD1 and PDL1 was reduced after two cycles of chemotherapy in SD group (P<0.05). The serum level of IL-6 and TGF-β was increased after two cycles of chemotherapy in PD group (P<0.05). IL-2 and TGF-β level was significantly increased after the targeted therapy(P<0.05).4. The high pretreatment IL-6 level implied a longer OS. The group with the active immune environment had a significantly longer OS trend compared with the immunocompromised group.The initial immune environment is an important factor affecting the OS. The reduction of IL-6 and PDL1 after treatment in immunocompromised group suggested a longer PFS compared with the increase. No significant association was found between the changes of seven cytokines after treatment and the OS in immunocompromised group. The changes of seven cytokines after treatment in active immune environment group also had no connection with PFS or OS.[Conclusions]Smoking and TNM staging are independent prognostic factors of PFS. The type of treatment is independent prognostic factor of OS. The imbalance immune environment deadlock is more likely to be break by the treatment and get the clinical PFS benefits. Selecting the appopriate strategy is the key point for these people. However, the poor prognosis casued by the immune status itself is difficult to reverse. The active immunization implies a better prognosis, but the whole immune environment is hard to break. Therefore, Avoid of excessive medical is more suitable for these people.