Predictive Value Of Cytokine Levels In Patients With Advanced Non-small Cell Lung Cancer Treated With Camrelizumab

Background: With the cross-penetration and rapid development of immunology and oncology,immunotherapy has changed the traditional treatment mode of many malignant tumors.Immmune checkpoint inhibitors（ICIs）are represented by programmed death-1（PD-1）and PD-1 ligand（PD-L1）inhibitors.It provides a new treatment idea for patients with advanced non-small cell lung cancer（NSCLC）,which improves the clinical symptoms and prolongs the survival time of patients to a certain extent,but the benefits are not universal.The occurrence of tumor is closely related to the state of the immune system of the body.Studies have shown that cytokines can not only reflect the immune state of the body but also regulate the immune response.Therefore,monitoring the changes of cytokine levels during the immunotherapy of tumor patients may be of certain significance to improve the efficacy of immunotherapy.Objective:To detect the serum cytokine levels and their changes during the treatment of lung cancer patients with ICIs,to explore the predictive value of cytokines for the efficacy of immunotherapy in patients with NSCLC,and to provide reference for clinical diagnosis and treatment of patients with lung cancer.Methods: Forty patients with advanced NSCLC treated with carrelizumab in the Oncology Department of Dongfeng General Hospital of Sinopharm from July 2020 to October 2021 were selected,and another 35 healthy subjects were selected as healthy control group.All NSCLC patients were evaluated according to solid Tumor Response Assessment Criteria（RECIST）version 1.1 after 2 cycles of carrelizumab treatment;The serum levels of cytokines IL-2,IL-4,IL-6,IL-8,IL-10,IFN-γ and TNF-α were determined by flow cytometry.Statistical software SPSS25.0 was used to analyze the correlation of serum cytokine level and its change rate with the efficacy and prognosis of immunotherapy.Result:1.Evaluation of the efficacy of immunotherapy in lung cancer patients: among 40 patients,7 patients achieved partial response（PR）after carrelizumab treatment;There were 20 patients with stable disease（SD）and 13 patients with progressive disease（PD）.Patients with PR+SD were assigned to the control group（n=27）and patients with PD were assigned to the progressive group（n=13）.2.Comparison of serum cytokine levels between the NSCLC group and the healthy control group: Compared with the healthy control group,serum IL-8 and TNF-αlevels in the NSCLC group were increased and the differences were statistically significant（P< 0.05）;the other five Cytokines: The expression levels of IL-2,IL-4,IL-6,IL-10,and IFN-γ were changed compared with the healthy control group,but there was no statistically significant difference（P>0.05）.3.The relationship between the general data of NSCLC patients and the efficacy of immunotherapy: age,gender,ECOG PS score,pathological type,stage,smoking history and brain metastasis had no significant correlation with the efficacy of immunotherapy（P > 0.05）.4.Studies on the correlation between serum cytokine levels and the efficacy of immunotherapy in lung cancer patients:There was no significant difference in the serum levels of initial cytokines between the control group and the progression group before immunotherapy（P>0.05）.After 2 cycles of immunotherapy,the serum IL-8 level in the control group was lower than that in the progression group when the efficacy was first evaluated（P<0.05）.The other factors were IL-2,IL-4,IL-6,IL-10,IFN-γ,TNF-αlevels had no significant difference.5.Comparison of the dynamic changes of cytokines between the two groups before and after treatment:The change rate of IL-8 in the control group was significantly lower than that in the progression group,and the difference was statistically significant（P<0.05）.5.After logistic regression,it was proved that the change rate of IL-8 level was correlated with the efficacy of camrelizumab treatment（P<0.05）,which was an independent factor affecting the efficacy of immunotherapy in patients with non-small cell lung cancer.6.After drawing the ROC curve,it was concluded that the area under the ROC curve（AUC）was 0.724>0.5,indicating that the change rate of IL-8 had a certain predictive value for the efficacy of immunotherapy in patients with NSCLC;and the95% confidence interval was 0.549-0.898,Youden The index is 38.5%,and the cut-off value is 22%7.Correlation study between IL-8 change rate and survival prognosis:The overall survival OS was included for survival analysis.The low change rate group,that is,the NSCLC patients whose serum IL-8 change rate was lower than 22%,had a longer overall survival.Conclusion: Cytokines are closely related to the occurrence and development of lung cancer.Compared with healthy people,the levels of cytokines in NSCLC patients have certain changes.During treatment with PD-1/PD-L1 immunosuppressants,The change rate of IL-8 level is an independent factor affecting the efficacy of camrelizumab in the treatment of advanced NSCLC patients;the change rate of IL-8 level may have a certain predictive value for efficacy,and may also be related to the survival prognosis of patients.Lung cancer patients with an IL-8 change rate of less than 22% had longer OS.