| Purpose:Given that most patients are less reactive when receiving immunotherapy targeting immune checkpoints(ICP),it is particularly important to choose a suitable time to add immunotherapy.The purpose of this study was to clarify the changes in peripheral blood tumor immunotherapy reactivity-related markers during the treatment of epithelial ovarian cancer(EOC),thus providing a basis for exploring the timing of the addition of immunotherapy.Materials and Methods:1.Indicator selection: Through the literature search,we determined the ICPi treatment reactivity related markers in peripheral blood to our study.As ICPi availability markers,absolute lymphocyte count(ALC),absolute eosinophil count(AEC)and gamma interferon(IFN-γ)were positively correlated with the therapeutic reactive.As ICPi ineffective markers,absolute neutrophil count(ANC),absolute mononuclear count(AMC),neutrophil count/lymphocyte ratio(d NLR),soluble interleukin-2 receptor(s IL-2rα,s CD25)and interleukin-6(IL-6)were negatively correlated with the therapeutic reactive.2.patient inclusion: retrospective collection of EOC patients admitted at wuhan concord hospital from march 1,2016 to march 1,2019.Patients with othertumors,chronic inflammatory diseases or autoimmune diseases were excepted.3.data collection: General information of patients,clinicopathological data,course of diagnosis and treatment,and blood routine results of patients before and after surgery and chemotherapy were collected.CA125、ALC、AEC、AMC and ANC values were recorded.4.ELISA detection: use ELISA to detect the expression levels of s CD25(s IL-2Rα),IL-6,IFN-γ in peripheral blood5.Statistical analysis:T-test and non-parametric tests were used to compare whether the changes in the treatment process were statistically significant.Results:1.A total of 92 EOC patients were enrolled in the study,with an average age of 51 years,22 in FIGO stage I,15 in stage II,50 in stage III,5 in stage IV,72 in pathological type of high-grade serous carcinoma and 20 in other pathological types.There were 57 cases underwent primary debulking surgery(PDS)and 35 cases underwent interval debulking surgery(IDS).All chemotherapy regimens were combined with paclitaxel carboplatin.the median course of postoperative chemotherapy was 6,up to 11,and at least 4.2.As ICPi efficacy biomarkers,the ALC and AEC of postoperative were significantly decreased compared to preoperative levels(P<0.001,P=0.001),while the ANC 、 AMC 、 d NLR 、 IL-6 and s CD25 of ineffective biomarkers were significantly increased(P<0.05).3.As ICPi efficacy biomarkers,the ALC and AEC were significantly increased after chemotherapy compared to post-operative levels(P=0.027,P<0.001),and the ANC、AMC、d NLR、IL-6 and s CD25 of ineffective biomarkers were significantly decreased(P<0.05).4.In 57 patients with primary debulking surgery(PDS),the ANC,AMC and d NLR after operation were significantly higher than those before operation(P<0.001).In contrast,ALC and AEC were significantly lower than that before operation(P<0.001).ANC 、 AMC and d NLR after first chemotherapy were significantly lower than those after operation(P<0.001)and the AEC after first chemotherapy was significantly higher than those after operation(P<0.001),and the ALC was not significantly higher(0.99 VS 1.04,P= 0.122).No significant difference(P >0.05)were found after the second chemotherapy.And no significant change in the other chemotherapy.5.In 35 cases of the ovarian epithelial tumor with Interval debulking surgery(IDS),the ANC and d NLR after operation were significantly higher than those before operation(P <0.001),while ALC and AEC were significantly lower than that before operation(P <0.001,P = 0.02),and the increase of AMC was not significant(0.5 VS 0.5,P = 0.96).After the first operation,the first chemotherapy significantly lower the ANC,AMC and d NLR(P <0.001),and the ALC and AEC did not change significantly;After the second radical operation,the AMC and d NLR were significantly higher than that before radical operation(P = 0.033,P =0.003),and ALC was significantly reduced before radical operation(P <0.001),while the change of ANC and AEC did not have significant statistical significance.The ANC,AMC,d NLR of the first chemotherapy after radical operation was significantly lower than that after operation(P < 0.001),AEC was higher(P=0.01)while ALC was not significantly higher.There was no significant difference in ANC,ALC,AMC,d NLR between the second chemotherapy and the first chemotherapy after radical operation(P>0.05).Conclusion:As the ICPi treatment effectiveness markers,the level of ALC and AEC was decreased after surgery while the ANC 、 AMC 、 d NLR 、 s CD25 and IL-6 of ineffective biomarkers were significantly increased.After one course of chemotherapy,ALC 、 AEC was increased while ANC 、 AMC 、 d NLR and peripheral blood s CD25、IL-6 was decreased.The effect of more chemotherapy on the above indexes was not obvious.Different surgical methods will have a certain impact on the changes of the above indicators in the course of treatment.Those suggests that immediate addition of ICPi treatment after operation is inappropriate and should be re-used after at least one course of adjuvant chemotherapy ICPi treatment may result in better therapeutic reactivity. |
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