The Study Of The Correlation Between PD-L1 Combined With CD8~+T/Tregs Cells And The Efficacy Of Immunotherapy For Advanced Triple-negative Breast Cancer

Purpose:To explore the value of PD-L1 expression status combined with CD8~+T/Tregs cells and the changes of T cells in peripheral blood in predicting the short-term efficacy and prognosis of patients with advanced triple-negative breast cancer after immunotherapy combined with chemotherapy,as well as the correlation with adverse reactions and quality of life.Methods:Eighty patients with PD-L1-positive(CPS score≥10)advanced triple-negative breast cancer admitted to Yantai Yuhuangding Hospital from September 2019 to February2021 were collected,and all patients included in the study received immunotherapy combined with chemotherapy.Their specimens were immunohistochemically examined and divided into two groups according to the CD8~+T/Tregs ratio(ratio≥2 defined as positive).Positive PD-L1 expression and high ratio of CD8~+T/Tregs cells in the study group compared with positive PD-L1 expression and low ratio of CD8~+T/Tregs cells in the control group.Peripheral blood was collected from patients before and after treatment,and T cells were analyzed by flow cytometry in peripheral blood.Efficacy evaluation and follow-up prognosis according to RECIST 1.1 and recording the occurrence of adverse reactions.To evaluate the difference in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)between the two groups.Adverse reactions occurring in both groups were recorded and graded using Common Terminology Criteria for Adverse Events version 5.0.The World Health Organization Quality of Life(WHOQOL)-100 scale was used to compare the quality of life of patients in the two groups after treatment.The relationship between immunohistochemical and flow cytometric parameters and efficacy,prognosis and immune-related adverse reactions,and quality of life after treatment was analyzed.Result:Efficacy evaluation of the 80 patients included in the study revealed that the ORR and DCR in the study group were significantly higher than those in the control group(ORR:60%vs 35%,p=0.022;DCR:85%vs 60%,p=0.011).The short-term follow-up results showed that the middle PFS of the study group(9.8 months,95%confidence interval 8.5months-11.3 months)was significantly longer than that of the control group(5.9 months,95%confidence interval 5.4 months-9.5 months)by 3.9 months(p=0.001).The OS,another study endpoint,had not been reached at the end of the study,but the 1-year OS in the study group was 87.5%,15%higher than that of the control group(72.5%),which was not statistically significant(p=0.081).Flow cytometry of peripheral blood T cells before and after treatment revealed that the CD8~+T/Tregs cell ratio in peripheral blood before and after treatment was not significantly correlated with ORR,DCR and PFS,and did not affect the incidence of immune-related adverse reactions.However the 1-year OS rate of patients in the group with positive CD8~+T/Tregs ratio in peripheral blood after treatment can be significantly prolonged(90%vs70%,p=0.024).During the study,the incidence of immune-related adverse reactions was 70%,and there was no significant difference in the incidence of immune-related adverse reactions between the two groups.Immune-related adverse reactions mainly include reactive capillary hyperplasia,aspartate aminotransferase increased,alanine aminotransferase increased,hypothyroidism,asthenia,anemia,bilirubin increased,proteinuria,pyrexia,leukopenia.Adverse reactions were mainly grade 1-2,and the incidence of grade≥3 adverse reactions was 10%.During the study period,no deaths events due to serious immune-related adverse reactions during the study.The quality of life of the two groups was evaluated after treatment using the World Health Organization Quality of Life-100 Scale.The scores of all domains and the total score in the study group were significantly higher than those in the control group(p<0.05),indicating that the quality of life in the study group was significantly better than that in the control group after treatment.Conclusion:1.CD8~+T/Tregs ratio combined with PD-L1 expression status can predict the efficacy and prognosis of immunotherapy combined with chemotherapy in patients with advanced TNBC,which is the dominant population for immunotherapy combined with chemotherapy screening.When the CD8~+T/Tregs ratio is≥2 and PD-L1 CPS score is≥10in TNBC patients,the choice of immunotherapy combined with chemotherapy regimen has significant clinical benefit compared with other populations,and does not increase the occurrence of adverse events on the basis of prolonging progression-free survival,which can effectively improve the quality of life of patients.2.Correlation analysis of peripheral blood CD8~+T/Tregs cell ratio before and after treatment with the above indicators.Elevated CD8~+T/Tregs cell ratio in peripheral blood after treatment prolongs the 1-year OS rate in patients with advanced TNBC.