VEGF-A Is Associated With the Degree of TILs and PD-L1 Expression in Primary Breast Cancer

Abstract

Background/Aim: Vascular endothelial growth factor-A (VEGF-A), an important angiogenic factor, has been reported to effect cancer growth and development. Recent reports indicated that anti-VEGF therapy has an important effect of enhancing anti-tumor immunity in various cancers. In the current study, we investigated the relationship between VEGF-A expression and immunological factors, including programmed cell death ligand 1 (PD-L1) and the degrees of stromal tumor-infiltrating lymphocytes (TILs) in breast cancer. Patients and Methods: This study enrolled 97 cases with invasive breast cancer who had undergone surgery without preoperative therapy. The grades of stromal-TILs were evaluated using the criteria of the International Working Group for TILs in breast cancer: low, intermediate, and high. VEGF-A and PD-L1 positivity were evaluated by immunohistochemistry. The relationship between VEGF-A expression and the expression of PD-L1 and TILs was investigated. Results: Among the 97 cases, 37 (38.1%) had positive VEGF-A expression in the breast tumor. We divided the cases in two groups based on the VEGF-A expression levels. The analysis revealed that PD-L1 positivity was significantly associated with VEGF-A expression in the breast tumor (29.7% vs. 10.0%, p=0.014). Among the cases with positive PD-L1, 36.7% of VEGF-positive cases and none of VEGF-negative cases had low TILs in the breast tumor. Conclusion: VEGF-A expression in breast cancer may reflect PD-L1 expression in the tumor. VEGF-A may act as a negative biomarker of TILs in PD-L1-positive breast cancer. Our results suggest that VEGF-A may be predictive of immunological features and may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

“…Hypoxia-mediated angiogenesis is associated with immune tolerance [ 86 ]. Hypoxia induces expression of VEGF, which inhibits dendritic cell maturation [ 87 , 88 ]; VEGF in turn enhances PD-L1 expression in dendritic cells, downregulating T cell function [ 89 – 91 ]. In addition, CD47 expression is related to HIF1A target VEGF.…”

18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Predicts Tumor Immune Microenvironment Function in Early Triple-negative Breast Cancer

“…Previously, we reported that TIL scoring based on FDG PET/CT was related to pCR (37), and scoring the CD8/FOXP3 ratio might predict a pCR more accurately. PD-L1 is expressed on cancer cells and tumor-infiltrating macrophages by IFN-γ and suppresses VEGF expression and T-cell activity via the PD-1/PD-L1 pathway (38). Immune checkpoint inhibitors that block the PD-1/PD-L1 pathway have been demonstrated to improve progression-free survival and the pCR rate following neoadjuvant chemotherapy administered for TNBC (30,39,40).…”

Comprehensive Computational Analysis of Honokiol Targets for Cell Cycle Inhibition and Immunotherapy in Metastatic Breast Cancer Stem Cells

“…Previous studies have shown that high expression levels of HSP90 (HSP90α and HSP90β) increase the likelihood of recurrence and distant metastases in triple negative and ER+/HER2-breast cancer, and are associated with higher mortality [69]. Overexpression of HSP90 in human breast cancer cells has been linked to enhanced cell proliferation [42] and metastasis, [70] as well as to short OS and aggressive clinicopathological characteristics, such as high clinical stage, large tumors, and lymph node involvement [71]. Lin et al reported that elevated HSP90AB1 expression was linked to a better overall survival of ER-and Basal-like breast cancer patients [55].…”