Prognostic implication of PD-L1 expression and associated tumor infiltrating lymphocytes in metastatic breast cancer

Abstract

Introduction: One of the most important regulators of immune response is the programmed death receptor 1 (PD-1) and its interaction with its ligand (PD-L1), which negatively influences the immune response. Objectives: This study aims to clarify PD-L1 expression levels and the associated tumor infiltrating lymphocytes (TILs) in patients with metastatic breast cancer, and to assess their influence on the prognosis of these patients and the association with clinico-pathologic criteria. Patients and Methods: PD-L1 expression was analyzed using immunohistochemistry (IHC) while TILs count was assessed by histopathological examination of the hematoxylin and eosin (H & E) stained full tumor sections from 50 patients diagnosed with stage IV breast cancer at Ain Shams University hospital, Cairo, Egypt. Results: PD-L1 expression was demonstrated on TILs in 21 of 50 specimens, and on tumor cells in 13 of 50 specimens. Triple negative breast cancer (TNBC) and ER-/Her2+ subtypes were significantly associated with TIL infiltration and PD-L1 expression (on TILs and tumor cells). High TIL infiltration was significantly associated with worse overall survival (OS) and progression free survival (PFS) (P=0.0238 [HR 4.7, 95% CI: 1.22-18.11] and P=0.0262 [HR 3.1, 95% CI: 1.14-8.59] respectively). No correlation was found between PD-L1 expression (on tumor or TILs) and the survival of the patients (OS nor PFS). Conclusion: High TIL count infiltrating the breast tumor is associated with worse OS and PFS in patients with metastatic breast cancer. High PD-L1 expression correlated with high counts of TIL levels around the tumor. These findings have major clinical implications in using immune-checkpoint inhibitors in treating breast cancer patients.

The various role of microRNAs in breast cancer angiogenesis, with a special focus on novel miRNA-based delivery strategies

“…Even if a particular miRNA is successfully targeted, there may still be unintended side effects [293]. One strategy to get around this problem is to utilize small amounts of combined miRNAs that work together to control the expression of the same target gene [294,295].…”

Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment

“…A binary vector including an OAd and a helper-dependent Ad (HDAd; combinatorial Ad vector (Cad)) that expresses checkpoint PD-L1 blocker and IL-12 has been demonstrated by this work to be systemically delivered by MSCs [ 198 ]. The immune checkpoint ligand PD-L1 has been found to be overexpressed in a variety of solid tumors [ 199 ]. PD-L1 binds to its receptor PD-1, and blocking it has shown therapeutic potential in cancer therapy [ 200 ].…”