Relationship Between Cytokines Levels And Efficacy Of Anti-PD-1 Immunotherapy In Non-Small Cell Lung Cancer

Objective:Interleukins,TNF-α and INF-γ play a great role in the process of immune cells killing tumor cells,especially in the evasion and tolerance of tumor to immunotherapy.The aim of this study is to investigate the clinical significance of interleukin(IL),TNF-α and INF-γ in non-small cell lung cancer(NSCLC)immunotherapy by detecting the changes in serum levels of TNF-α and INF-γbefore and after PD-1 inhibitor immunotherapy,and to explore the predictive value of IL,TNF-α and INF-γ in NSCLC immunotherapy.Methods:In this study,Flow cytometry was used to detect the serum levels of IL-4,IL-6,IL-10,IL-17,TNF-α and INF-γ in 42 patients with advanced NSCLC who received four cycles of PD-1 inhibitor immunotherapy.Mann-Whitney U test was used to analyze whether there were differences in serum levels of IL-4,IL-6,IL-10,IL-17,TNF-α and INF-γ before immunotherapy in NSCLC patients with different clinical characteristics such as age,gender and pathological types.Changes in serum levels of IL-4,IL-6,IL-10,IL-17,TNF-α and INF-γ before and after immunotherapy in NSCLC patients were analyzed using Mann-Whitney U test.Mann-Whitney U test and chi-square test were used to compare the efficacy of immunotherapy in different groups.The Kaplan-Meier survival analysis curve was drawn,and the differences between survival curves were compared by Logrank test.Cox proportional hazards regression model was used to analyze the risk factors affecting the prognosis of NSCLC patients.Results:(1)In 42 NSCLC patients included in this study,the median expression level of IL-4 after immunotherapy was 1.74(0.68,3.97),which was higher than1.04(0.37,2.08)before immunotherapy,and the median expression level of IL-17 after immunotherapy was 5.78(1.69,10.98)pg /ml was significantly lower than that before immunotherapy [7.9,(4.44,12.42)pg/ml,P < 0.05].There were no significant differences in the expression levels of IL-6,IL-10,TNF-α and INF-γbefore and after immunotherapy(P > 0.05).(2)The expression level of IL-4 in female patients before immunotherapy was higher than that in male patients,and the difference was statistically significant(P < 0.05).There was no significant difference in IL-4 level between different age and pathological types before immunotherapy(P > 0.05).There was no significant difference in the expression levels of IL-6,IL-10,IL-17,TNF-α and INF-γ in serum of patients with different gender,age and pathological types before immunotherapy(P > 0.05).(3)After 4cycles of PD-1 inhibitor immunotherapy,31 patients were included in the effective group and 11 patients were included in the ineffective group.In the effective group,the median level of serum IL-17 after immunotherapy was 3.86,(1.34,10.7)pg/ml,which was lower than 9.46,(2.39,12.9)pg/ml before treatment.The difference was statistically significant(P < 0.05).There was no significant difference in the ineffective group before and after immunotherapy(P > 0.05).There were no significant differences in the expression levels of IL-4,IL-6,IL-10,TNF-α and INF-γ between the two groups(P > 0.05).(4)In 42 patients who received immunotherapy,changes in the expression levels of IL-17 and TNF-αwere correlated with the efficacy of immunotherapy.(5)Among the 42 patients who received immunotherapy,PFS was 6.5 months(95%CI:4-10),and increased IL-17 expression level was associated with lower PFS.Conclusion:PD-1 inhibitors caused changes in the expression levels of IL-4 and IL-17 in patients with effective treatment.The increased expression of IL-17 after immunotherapy may provide certain reference value for the treatment effect and PFS of advanced NSCLC.