Decoding the tumor microenvironment of triple-negative breast cancer: from immune evasion to precision immunotherapy

Abstract

Triple-negative breast cancer (TNBC) represents a highly aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, resulting in limited targeted therapeutic options and poor clinical outcomes. Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of TNBC, therapeutic responses remain restricted to a subset of patients due to substantial heterogeneity within the tumor immune microenvironment (TIME). Increasing evidence indicates that immune evasion in TNBC is driven by complex interactions among tumor cells, immune populations, stromal components, and metabolic alterations. This review summarizes the dynamic landscape of the TNBC immune microenvironment, focusing on the functional roles of tumor-infiltrating lymphocytes, tumor-associated macrophages, tumor-associated neutrophils, natural killer cells, and myeloid-derived suppressor cells in regulating antitumor immunity and therapeutic resistance. We further discuss clinical advances of ICIs, including monotherapy and chemoimmunotherapy approaches, as well as emerging therapeutic strategies involving small molecules, bispecific antibodies, antibody–drug conjugates, and novel immune-based modalities.