Abstract
Objective: Changes in the number of various tumor-infiltrating lymphocytes (TILs) and degrees of vascular normalization in breast cancer (BC) patients after neoadjuvant chemotherapy (NAC) were analyzed to screen key factors that can predict the prognosis.Methods: HE-stained sections were used to assess the degree of TILs infiltration; immunohistochemically stained sections were used to assess the infiltration of CD8+, CD4+, FOXP3+ Tregs and the expression of PD-L1; immunofluorescence-stained sections were used to assess the microvessel density (MVD) and microvessel pericyte coverage index (MPI). The expression of them before NAC were compared with those after NAC, and correlations between changes in these parameters and the pathological complete remission (pCR) and DFS of BC patients were analyzed.Results: After NAC, the percentage of patients with enhanced sTILs in the pCR group was significantly higher than that in the Non-pCR group (P < 0.05). Univariate and multivariate analyses showed that the number of FOXP3+ Tregs and MPI before NAC were correlated with pCR (P < 0.05). Survival analysis showed that the DFS of BC patients with reduced FOXP3+ Tregs was significantly better than that of patients with elevated FOXP3+ Tregs (P = 0.029). The sTILs count and MPI were significantly higher in primary tumors than lymph nodes (P < 0.05).Conclusion: After NAC, the reduced infiltration of FOXP3+ Tregs was correlated with an improvement in DFS in BC patients. Changes in the number of FOXP3+ Tregs and the MPI may be used as prognostic markers for BC patients.
Highlights
Among females, breast cancer (BC) is the malignant tumor with the highest incidence [1] and seriously threatens the health of women worldwide [2]
Patients with HER2-positive BC accounted for 28.0% (n = 21), patients with luminal/HER2negative BC accounted for 29.3% (n = 22), patients with luminal/HER2-positive BC accounted for 18.7% (n = 14), and patients with triple-negative breast cancer (TNBC) accounted for 24.0% (n = 18)
Based on the number of stromal TILs (sTILs), CD8+ T cells, CD4+ T cells, and FOXP3+ Tregs and the PDL1 expression, MVD, and MPI values before and after Neoadjuvant chemotherapy (NAC), our study found that after NAC, sTILs, CD8+ T cells, CD4+ T cells, and MPI were increased in tumor tissue, and FOXP3+ Tregs, programmed death ligand 1 (PD-L1) expression, and MVD were decreased in tumor tissue (Figure 2A)
Summary
Breast cancer (BC) is the malignant tumor with the highest incidence [1] and seriously threatens the health of women worldwide [2]. Neoadjuvant chemotherapy (NAC) is currently the main treatment for locally advanced BC and it can be used to detect the sensitivity of tumor cells to anticancer treatment and to guide the follow-up treatment [6] Our understanding of these patients is still insufficient; recurrence and metastasis still occur in patients who achieve pCR after NAC. Denkert divided BC patients into three groups according to sTILs infiltration in tumor tissues: low sTILs infiltration (0–10%), medium sTILs infiltration (11–59%) and high sTILs infiltration (60–100%), their studies suggested that high sTILs infiltration can predict the NAC response of all BC subtypes and is correlated with the survival benefit of Her2-positive BC and triple-negative breast cancer (TNBC) [14]. Programmed death-1 (PD-1) expressed by TILs binds to PD-L1 expressed on tumor cells to allow tumors to escape anti-tumor immunity in the TME of BC [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
