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

Abstract

lobally, breast cancer is the second most frequently diagnosed malignancy just behind lung cancer, accounting for over two million cases each year, and the fourth cancer causing death worldwide; the leading cause of cancer death though in females, with around 600,000 deaths each year (Bray et al., 2018). Cancer immunotherapy through the inhibition of negative immune regulators, or checkpoints, represents a major milestone in cancer therapy. Of the most common immune checkpoints to be targeted is the programmed cell death protein 1 (PD-1) and its ligand (PD-L1). The measurement of these two biomarkers is used as a prognostic and predictive marker to the cancer immunotherapy with checkpoint inhibitors (Zerdes et al., 2018). Inhibitors of PD-1 and PD-L1 have been shown to significantly improve patient outcomes in different types of immunogenic cancers such as non-small cell lung cancers (NSCLC), malignant melanoma, renal cell carcinoma (RCC), and some immunogenic breast cancer subtypes (Li & Gu, 2018; Schmid et al., 2018; Wang et al., 2017; Zhou et al., 2018). Breast cancer is composed of heterogenous subtypes, each has its specific pathologic and genetic characters, as well as different prognostic significance. Of these subtypes, triple negative breast cancer (TNBC) is the most immunogenic type, as it is rich in tumor infiltrating lymphocytes and PD-L1 co-expression (Sobral-Leite et al., 2018).