Effect Of PD-1 Inhibitor Combined With Chemotherapy On The Efficacy And T Cell Subsets Of Advanced Lung Cancer

Objective:To evaluate the clinical efficacy of PD-1 inhibitor(Camrelizumab or sintilimab)combined with chemotherapy in patients with advanced lung cancer,and its effect on peripheral blood T lymphocyte subsets and cytokines.And further explore whether peripheral blood T cell subsets and cytokines can become effective biomarkers that can predict the efficacy of immunotherapy.Methods:A total of 57 subjects were recruited in this study.Thirty seven patients with advanced lung carcinoma,treated in the Second Hospital of Jilin University from September 2021 to December 2022 were randomly separated into chemotherapy group(n=17)and combination group(n=20),and 20 healthy cases were recruited as the control group.The chemotherapy group received traditional chemotherapy alone,while the combination group were treated with Camrelizumab or sintilimab on the basis of chemotherapy additionally.Each group was treated for 4 cycles.Changes in the levels of cytokines prior to treatment were compared and analyzed in the combination group,chemotherapy group and control group.At the same time,the clinical efficacy and safety,the levels of T lymphocyte subsets and cytokines were compared and analyzed in the combination group and chemotherapy group.In addition,patients of the combination group evaluated as CR and PR were classified as immune response group,while patients evaluated as SD and PD were classified as immune non-response group.The values of T lymphocyte subsets and cytokines in the two groups were compared.Results:(1)There was no significant difference in age,sex and smoking between chemotherapy group,combination group and control group;the pathological type,EGCO scores and TMN stage between chemotherapy group and combination group were not significant,which was comparable(P > 0.05).(2)The value of TGF-β was not significant between the chemotherapy group,combination group and control group(P > 0.05).But the levels of IFN-γ,IL-2,IL-10 were statistically significant between the three groups(P < 0.05).Inter-comparison showed that compared with the control group,IFN-γ and IL-2 in peripheral blood of chemotherapy group and combination group were significantly decreased and IL-10 was significantly increased(P < 0.05),while the values of IFN-γ,IL-10 and IL-2 were not statistically significant between the two groups(P > 0.05).(3)The ORR of combination group and chemotherapy group were 55% and 20%respectively,which was statistically significant(P < 0.05).But the DCR was not statistically significant between the two groups(85% vs.60%,P > 0.05).(4)The values of IFN-γ,IL-2,TGF-β,IL-10 were not significant difference between the combination group and chemotherapy group before treatment(P >0.05).Compared with before treatment,the value of serum IL-2 in the combination group was increased after treatment,and the value of serum IL-10,IFN-γ,TGF-βwere decreased after treatment,with significant difference(P < 0.05).Compared with the chemotherapy group,the value of serum IL-2 post-therapy in combination group was significantly increased,and the values of serum IL-10,TGF-β were significantly decreased,which was statistically significant(P < 0.05).(5)There was no significant difference in peripheral blood T lymphocyte subsets(CD3+(%),CD4+(%),CD8+(%),CD4+/CD8+ and NK(%))between the chemotherapy group and combination group prior to treatment,(P > 0.05).Via 4courses of treatment,the levels of CD3+(%),CD4+(%),and CD4+/CD8+ were significantly increased,while the levels of NK(%)was significantly decreased compared to before treatment(P < 0.05).Compared with the chemotherapy group,the serum CD3+(%),CD4+(%),CD4+/CD8+ post-therapy in combination group were significantly higher(P < 0.05),while the levels of serum CD8+(%)and NK(%)were not significantly different(P > 0.05).(6)There are 20 patients in the combination group,with 12 patients in the immune responsive group and 8 patients in the immune non-responsive group group.Compared with the immune non-responsive group,the values of CD4+(%), CD4+/CD8+,IFN-γ,IL-2 were increased,and the values of IL-10,TGF-β were decreased in the immune responsive group,and which were statistically significant(P < 0.05).While the values of CD3+(%),CD8+(%)and NK(%)were not statistically significant between the two groups(P > 0.05).(7)There was no significant difference in the incidence of adverse reactions between the combination group and the chemotherapy group(P > 0.05).Conclusions:1、Compared with chemotherapy alone,significant therapeutic effects can be obtained in the treatment of advanced lung cancer with PD-1 inhibitors combined with chemotherapy,while not increasing adverse reactions during treatment.2、Inflammatory disorders in patients with advanced lung cancer.PD-1 inhibitors can regulate the peripheral blood T cell subsets and cytokine,and improve the cellular immune function and inflammatory response.3、Peripheral blood CD4+(%),CD4+/CD8+ and IFN-γ,IL-2,IL-10,TGF-β levels are related to the effect of immunotherapy,and are expected to become new predictors of immune efficacy.