Changes Of STILs And PD-L1 Before And After Neoadjuvant Chemotherapy And Its Relationship With DFS In Breast Cancer Patients

Objective By investigating the infiltration of sTILs and the expression of PD-L1 in breast cancer patients before and after neoadjuvant chemotherapy,we aimed to explore the effect of neoadjuvant chemotherapy on the tumor microenvironment of breast cancer,and further observe the value of the changes of sTILs and PD-L1 in the disease-free-survival of breast cancer patients following neoadjuvant chemotherapy.Methods We retrospectively collected the clinical data of 62 patients with breast cancer who received neoadjuvant chemotherapy,and selected core needle biopsy specimens before treatment and formalin fixed paraffin embedded blocks of surgical specimens after neoadjuvant chemotherapy.STILs were assessed on HE sections,while the infiltration of CD8+sTILs,CD4+sTILs,FOXP3+sTILs were assessed on immunohistochemical sections,as well as the expression of PD-L1 Then,we compared the changes of sTILs,CD8+sTILs,CD4+sTILs,FOXP3+sTILs and the expression of PD-L1 before and after neoadjuvant chemotherapy.Therefore,we could observe the relationship between these changes and the disease-free survival of breast cancer patients.Results The infiltration of sTILs,CD8+sTILs and CD4+sTILs was significantly increased after neoadjuvant chemotherapy in breast cancer patients(P < 0.05),while FOXP3+sTILs and PD-L1 were significantly decreased(P < 0.05).The decrease of FOXP3+sTILs after neoadjuvant chemotherapy was most obviously found in the type of Her2(3+)(P = 0.008)and Luminal-Her2(-)(P = 0.005)and Luminal-Her2(3+)(P = 0.004)breast cancer patients.Univariate and multivariate analysis showed that pre-treatment FOXP3+sTILs were associated with pCR following neoadjuvant chemotherapy.The DFS of breast cancer patients with reduced FOXP3+sTILs after neoadjuvant chemotherapy was significantly better than those with elevated FOXP3+sTILs(P = 0.012).After neoadjuvant chemotherapy,the infiltration of CD4+sTILs in residual tumors was higher than that in metastatic axillary lymph nodes(P = 0.001),while the expression of total sTILs,CD8+sTILs,FOXP3+TILs and PD-L1 was consistent(P > 0.05).Conclusion Neoadjuvant chemotherapy has changed the microenvironment of breast cancer.On the one hand,neoadjuvant chemotherapy increased the infiltration of anti-tumor immune effector cells in the microenvironment of breast cancer.On the other hand,the effect of neoadjuvant chemotherapy reduced the infiltration of FOXP3+sTILs and the expression of PD-L1.The reduced FOXP3+sTILs was more pronounced in the type of Her2(3+)and Luminal breast cancer patients,and was associated with improved DFS.Therefore,it may be a prognostic factor for breast cancer patients.