Gastric Cancer Immunoscore Correlates With Tregs、PD-L1、MMR And Relationship Between Tregs And Immune Efficacy

Objective:This experiment mainly studied the correlation between immunoscore of gastric cancer and Tregs density,PD-L1 expression,MMR status;To explore the consistency of Tregs density between biopsy specimens and surgical specimens;To explore the relationship between Tregs density and immune efficacy.Methods:From January 2019 to May 2022,96 gastric cancer tissue samples with preoperative biopsy and complete surgical specimens were collected.A total of 11 tissue specimens from advanced gastric cancer patients who underwent3 cycles of immunotherapy at our institution and underwent biopsy before immunotherapy were collected from January 2022 to may 2022.These 11 patients were all CPS≥5,p MMR,and HER2 negative,and the treatment regimen was XELOX(oxaliplatin+capecitabine)+Sintilimab,which was evaluated by im RECIST criteria for response.Immunoscore,density of Tregs,PD-L1 expression,and MMR status of 96 surgical samples were determined by immunohistochemistry(IHC);IHC was used to determine the density of Tregs in 96 biopsy samples;IHC was used to determine the density of Tregs in 11 advanced gastric cancer biopsy samples;SPSS25.0was used to analyze the correlation between immunoscore and the density of Tregs,PD-L1 expression,and MMR status;To analyze whether Tregs density was consistent in biopsy specimens and surgical specimen tissues;The relationship between the density of Tregs and immunotherapeutic efficacy was analyzed.Results:1.The expression rate of high immunoscore(I3～I4)in 96 surgical specimens of gastric cancer was 35.4%(34/96),including 21 cases of I3 and13 cases of I4;The percentage of patients with low immunoscore(I0～I2)expression was 64.6%(62/96),including 12 cases of I0,26 cases of I1,and 24 cases of I2.2.In this study,CPS=1 and CPS=5 were used as thresholds,CPS<1 was defined as PD-L1 low expression,1 ≤ CPS<5 was defined as PD-L1 moderate expression,and CPS≥5 was defined as PD-L1 high expression.In96 gastric cancer surgical specimens,PD-L1(CPS<1)was 41.7%(40/96),and PD-L1(CPS ≥ 1)was 58.3%(56/96),and there was no correlation between immunoscore and PD-L1(CPS<1,CPS ≥ 1)(r=0.14,P=0.17).PD-L1(CPS<5)was 74.0%(71/96),PD-L1(CPS≥5)was 26.0%(25/96),and there was a significant positive correlation between the immunoscore and PD-L1(CPS<5,CPS≥5)(r=0.404,P<0.001).3.d MMR was 14.6%(14/96)and p MMR was 85.4%(82/96)in 96 surgical specimens of gastric cancer;The immunoscore was negatively correlated with MMR status(r=-0.311,P=0.006),with high immunoscore generally exhibiting d MMR and low immunoscore generally exhibiting p MMR.4.The high density of Tregs was 43.75%(42/96)and low density was56.25%(54/96)in 96 surgical specimens of gastric cancer,and the high density of Tregs was 38.5%(37/96)and low density was 61.5%(59/96)in 96 biopsy specimens of gastric cancer.The density of Tregs in biopsy samples was highly concordant with the density of Tregs in surgical samples(kappa=0.635,P<0.001).5.There was a significant negative correlation between immunoscore and Tregs density(r=-0.434,P<0.001).High immunoscore was usually associated with low density of Tregs,while low immunoscore was usually associated with high density of Tregs.6.Among the 11 patients with advanced gastric cancer,6 patients had low density of Tregs,5 patients had high density of Tregs,These 11 patients were all PD-L1(CPS ≥5),p MMR,and HER2 negative,and the treatment regimen was XELOX(oxaliplatin+capecitabine)+Sintilimab,After 3 cycles of immunotherapy,the efficacy was evaluated according to im RECIST criteria.Among the 6 patients with low Tregs density,4 had partial response(PR),1 had stable disease(SD),and 1 had progressive disease(PD).The objective response rate(ORR)was 66.7%(4/6),and the disease control rate(DC)was 83.3%.Among the 5 patients with high-density Tregs,1 case had partial response(PR),2 cases had stable disease(SD),and 2 cases had progressive disease(PD).The objective response rate(ORR)was 20%(1/5),and the disease control rate(DCR)was 60%(3/5).The ORR of patients with low Tregs density was significantly higher than that of patients with high Tregs density,The difference was not statistically significant due to too few study cases(P=0.14).Conclusions:1.There was no correlation between immunoscore and PD-L1(CPS<1,CPS ≥ 1),immunoscore is significantly associated with PD-L1(CPS<5,CPS ≥ 5)and MMR,patients with PD-L1(CPS ≥ 5)and d MMR usually show high immunoscore.2.The density of Tregs in biopsy samples is consistent with the density of Tregs in surgical samples,and it is relatively feasible to measure the density of tumor Tregs by biopsy samples.3.There was a significant negative correlation between the immunoscore and the density of Tregs,and the density of Tregs was expected to replace the immunoscore in assessing the microenvironment status.Patients with low density of Tregs may benefit more from immunotherapy,and the combined detection of PD-L1 expression,MMR status,HER2 and Tregs density is expected to improve the accuracy of the prediction of immune efficacy.