PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences Are Emerging. A Literature Review

Abstract

Recently, the development of immunotherapy through the immune checkpoint blockade led to long-lasting responses in several types of cancers that are refractory to conventional treatments, such as melanoma or non-small cell lung cancer. Immunotherapy has also demonstrated significant improvements in various other types of cancers. However, breast cancer remains one of the tumors that have not experienced the explosion of immunotherapy yet. Indeed, breast cancer was traditionally considered as being weakly immunogenic with a lower mutational load compared to other tumor types. In the last few years, anti-PD1/PD-L1 (Programmed death-ligand 1) agents have been evaluated in breast cancer, particularly in the triple negative subtype, with promising results observed when delivered as monotherapy or in combination with conventional treatments. In this review, we will report the results of the most recent studies evaluating immune checkpoint inhibitors in breast cancer. In addition, we will discuss the concomitant development of possible biomarkers, which is required for improving the selection of patients with the highest probability of benefiting from these agents.

Keywords: PD1; PDL1; breast cancer; immunotherapy; triple-negative breast cancer.

Figure 1

The PD-1/PD-L1 pathway. PD-L2 (green) is expressed in antigen-presenting cells. PD-L1 (blue) is also expressed in tumor cells and in several immune cells (myeloid cells, TReg, endothelial cells). PD-L1 and PD-L2 inhibit T cells and NK cells (minus sign). IFNγ mediates the up-regulation of tumor PD-L1. Abbreviations: APC = antigen-presenting cell; MDSC = Myeloid-derived suppressor cell; NK cell = Natural Killer cell; TReg = Regulatory T cell; CAF = Cancer associated Fibroblast; Endoth cell = Endothelial cell; PD-1 = Programmed cell death-1; PD-L1/2 = Programmed cell death 1 ligand 1/2; TCR = T Cell Receptor; MHC = Major Histocompatibility Complex.