Predictive biomarkers of response to immunotherapy in triple-negative breast cancer - state of the art and future perspectives.

Abstract

Background: Immunotherapy by using immune checkpoint inhibitors (ICIs) heralded a new era in the treatment of patients with advanced triple-negative breast cancer (TNBC). Nevertheless, in a substantial proportion of TNBC patients, the clinical outcomes of ICIs treatment remain unpredict-able and proper bio-markers to identify tumors sensitive to immunotherapy are urgently needed. Currently, the most clinically relevant bio-markers used to predict efficacy of ICIs in patients with advanced TNBC remain the immunohistochemical analysis of programmed death-ligand 1 (PD-L1) expression, the assessment of tumor infiltrating lymphocytes (TILs) present in the tumor microenvironment (TME), and the evaluation of the tumor mutational burden (TMB). Emerging bio-markers related to activation of the transforming growth factor beta signaling pathway, the discoidin domain receptor 1, and thrombospondin-1 as well as other cellular and molecular factors present within TME, have the potential to be utilized as predictors of response to ICIs in the future.

Purpose: In this review, we summarize the current knowledge of mechanisms regulating PD-L1 expression, of the predictive value of TILs as well as of associated cellular and molecular components present in the TME in TNBC. Furthermore, TMB and emerging bio-markers with potential value in predicting efficacy of ICIs are discussed, and new therapeutic strategies will be outlined.