Predictive Value Of Lymphocyte Subsets And Cytokines On The Efficacy Of Immunotherapy In Advanced Malignancies

Background and objective:The advent of immunotherapy has changed the overall treatment paradigm for oncology patients and has led to significant efficacy.However,not all tumor patients can benefit from immune checkpoint inhibitors(ICIs)therapy.Currently,programmed death-ligand 1(PD-L1),microsatellite instability(MSI),and tumor mutational burden(TMB)are used as markers relevant for immunotherapy.These markers can be used to predict therapeutic efficacy,but there are limitations in their practical application.The search for predictive markers of therapeutic efficacy of ICIs is the focus of current research.It has been found that ICIs exert their anti-tumor effects mainly through"immune normalization"and regulation of the tumor microenvironment(TME).As important components of the TME,lymphocyte subsets and cytokines are involved in tumor immunotherapy,and both of them play dual roles of immune promotion and immune suppression in the TME due to different factors.In this study,we investigated the value of lymphocyte subpopulation and cytokine levels and their change rates during immunotherapy in predicting the outcome of patients with advanced malignancies treated with programmed death-1(PD-1)/PD-L1 inhibitors.Methods:Patients with advanced malignancies who received immunotherapy for the first time from November2021 to December 2022 at Jiaozuo City People’s Hospital,Henan Province were collected through the electronic medical record system as the observation group.Another 30 healthy cases were selected from our physical examination center as the control group.Patients who had undergone at least 4 consecutive cycles of immunotherapy were selected from the observation group and their general data were recorded.These patients were required to have blood drawn before and after 4 cycles of immunotherapy,and the levels of lymphocyte subsets and cytokines were measured by flow cytometry,and the changes in the values were recorded and the change rates of each index were calculated.The efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1(RECIST 1.1).A total of 38 patients with advanced malignancies were enrolled by these screening criteria.Patients were classified into complete response(CR),partial response(PR),stable disease(SD),and progressive disease(PD)based on the efficacy evaluation results of 4 cycles of treatment,and patients with efficacy evaluation of CR,PR,and SD were included in the control group,PR and SD were included in the control group,and patients with PD were included in the progressive group.The correlation between lymphocyte subpopulation and cytokine levels and the rate of change with the efficacy and prognosis of immunotherapy was analyzed.SPSS 27.0software was applied for statistical analysis,and the differences were statistically significant when P<0.05.Results:1.Lymphocyte subsets fraction1.1 Comparison with the healthy control group:the levels of CD4~+T lymphocytes and CD4~+/CD8~+in the observation group were lower than those in the healthy control group,while the levels of CD8~+T lymphocytes were higher than those in the healthy control group,and the difference was statistically significant(P<0.05);the levels of the remaining lymphocyte subsets were not statistically different compared with those in the healthy control group(P>0.05).1.2 Comparison of lymphocyte subsets levels between control and progressive groups:There was no statistical difference in lymphocyte subsets levels between control and progressive groups before immunotherapy(P>0.05).The level of CD4~+T lymphocytes in the control group was higher than that in the progressive group after 4 cycles of immunotherapy,and the difference was statistically significant(P<0.05),while there was no statistical difference between the levels of lymphocyte subsets in the remaining two groups(P>0.05).1.3 Comparing the change rate of lymphocyte subpopulations in different efficacy groups,the change rate of CD4~+T lymphocytes in the control group was higher than that in the progressive group,and the difference was statistically significant(P<0.05),and there was no statistical difference in the change rate of lymphocyte subpopulations between the other efficacy groups(P>0.05).1.4 One-way logistic regression analysis showed that elevated levels of CD4~+T lymphocytes after immunotherapy were an independent influencing factor on the efficacy of PD-1/PD-L1 inhibitor treatment in patients with advanced malignancies to achieve disease control.1.5 The predictive ability of CD4~+T lymphocyte change rate on the efficacy of immunotherapy was assessed using the receiver operating characteristic curve(ROC)with an area under the curve(AUC)of0.717,a best cut-off value of 10.53%The sensitivity was 75.0%and the specificity was 64.3%,which were statistically different(P<0.05).1.6 Relationship between CD4~+T lymphocyte change rate and survival prognosis:Progression-free survival(PFS)was later included in the survival analysis,and the PFS was longer in the high change rate group,patients with CD4~+T lymphocyte change rate higher than 10.53%.2.Cytokines fraction2.1 Comparison with the healthy control group:the levels of IL-6,IL-10 and TNF-αwere higher in the observation group than in the healthy control group,and the difference was statistically significant(P<0.05);the levels of the remaining cytokines were not statistically different compared with the healthy control group(P>0.05).2.2 Comparison of cytokine levels between control and progressive groups:There was no statistical difference between cytokine levels in control and progressive groups before immunotherapy(P>0.05).After 4 cycles of immunotherapy,the IL-6 level in the progressive group was higher than that in the control group,and the difference was statistically significant(P<0.05),and there was no statistical difference between the cytokine levels in the remaining two groups(P>0.05).2.3 Comparison of cytokine change rates in different efficacy groups,IL-6 change rate in the progressive group was higher than that in the control group,and the difference was statistically significant(P<0.05),and there was no statistical difference in the comparison of cytokine change rates between the remaining different efficacy groups(P>0.05).2.4 One-way logistic regression analysis showed that the reduction of IL-6 level after immunotherapy was an independent influencing factor for the efficacy of advanced malignancy patients receiving PD-1/PD-L1 inhibitors to achieve disease control.2.5 The ROC curve was used to assess the predictive ability of IL-6 change rate on the efficacy of immunotherapy,and the AUC was 0.708,the best cut-off value was 43.59%,the sensitivity was 71.4%,and the specificity was 70.8%,which was statistically different(P<0.05).2.6 Relationship between IL-6 change rate and survival prognosis:PFS was included later for survival analysis,and patients in the low change rate group,with IL-6 change rate lower than 43.59%,had longer PFS.Conclusions:1.Lymphocyte subsets and cytokines are closely related to tumor development,and there are changes in lymphocyte subsets and cytokine levels in patients with advanced malignancies compared with healthy populations.2.The rate of change of CD4~+T lymphocytes and the rate of change of IL-6 may be predictive of the efficacy of treatment with PD-1/PD-L1 inhibitors in patients with advanced malignancies.3.CD4~+T lymphocyte change rate as well as IL-6 change rate may also correlate with the survival prognosis of patients,with longer PFS for patients with CD4~+T lymphocyte change rate higher than 10.53%and longer PFS for patients with IL-6 change rate lower than 43.59%.