Correlation Of Serum Immune-related Cytoki Ne Levels Between Efficacy And Prognosis In Patients With Advanced Non-small Cell Lung Cancer During Anti-PD-1 Therapy

[Objective]Immunological checkpoint inhibitors(ICIs)immunotherapy is more effective than traditional treatments,and the success of adverse reactions can significantly expand the range of treatment options for patients with non-small cell lung cancer(NSCL C).Effector T cells and their anti-tumor activity are activated by blocking PD-L1(programmed death ligand 1)or PD-1(programmed death 1)on infiltrating immune cells on tumor cells.Cytokines play an important role in the microenvironment of tumor tissues and the development of tumor cells.The dynamic monitoring of immune-related cytokines can help to understand the development of tumor tissues,evaluate the immune treatment effect and immune status of patients,with a view to Accurately screen out patients who can benefit from immunotherapy to achieve more accurate individualized immunotherapy.[Methods]From February 2017 to February 2018,41 patients with advanced non-small cell lung cancer who were treated with anti-PD-1 in the Department of Oncology,General Hospital of Chinese PLA,and 35 normal controls were selected from healthy subjects.All patients received at least 2 cycles of PD-1 inhibitor treatment,and Luminex(27-Plex)kit was used to detect the concentration of 27 cytokines in peripheral blood,and continued to be used until tumor progression or intolerable ad verse reactions occurred;SPSS22.0 software for statistical analysis,P<0.05 for t he difference was statistically significant.[Results]1.The initial serum levels of IL-8,IL-9,IL-15,Eotaxin,IP-10,MIP-1a,MIP-1b,RANTES and TNF-a in the lung cancer group were significantly higher than those in the normal control group and IL in the lung cancer group.The initial serum levels of-1ra,IL-2,IL-5,IL-10,IL-17,Basic FGF,GM-CSF and MCP-1 were significantly lower than those of the normal control group2,41 patients with lung cancer were divided into the disease control(DCR)group of 28 patients(including 7 PR and 21 SD)according to the results of the first evaluation.The disease progression(PD)group consisted of 13 patients.The levels of serum IL-1ra and MCP-1 in the DCR group were higher than those in the PD group,and the P value was close to 0.05,but the difference was not statistically significant(P<0.05).The other initial cytokine concentrations in the two groups were not significant.Difference(P>0.05).3.The levels of serum MCP-1 and TNF-a in patients with DCR group were significantly higher than those in PD group(P<0.05).4.Comparing the rate of change of cytokine levels in the first evaluation of efficacy(the difference between the level of the initial evaluation minus the initial level/initial level),the rate of change of serum TNF-a level in the DCR group was significantly higher than that in the PD group.There was a significant increase trend,the difference was statistically significant(P<0.05);the other cytokines increased or decreased during the immunotherapy,but the overall trend showed a rising or stable trend,and the rate of change of cytokine levels in different efficacy groups was not significant.Difference(P>0.05).5.Logistic regression analysis showed that the elevated level of TNF-a after immunotherapy was an independent influencing factor for the treatment of anti-PD-1 in patients with advanced lung cancer.6.The ROC curve was used to evaluate the disease control of TNF-a change rate,and the cutoff value of TNF-a change rate was 30.0%,that is,when the patient increased the amplitude,the disease control state was evaluated.The sensitivity was 60.9%,the specificity was 84.6%,and the Yoden index was 45.3%.7.COX single factor and multivariate analysis showed that patients with advanced non-small cell lung cancer were treated with immunotherapy for patients with third-line or higher PFS shortening,and patients with TNF-a change rate of less than 30%had shorter PFS.[Conclusions]In the anti-PD-1 treatment,some peripheral blood immune-related cytokine levels and concentration changes may be related to the efficacy of immunotherapy,and may be related to survival prognosis.This study was used as a preliminary exploratory study and the results also required a large sample of prospective clinical trials to validate.