The heterogeneous and dynamic immune-tumor interface in breast cancer
Breast cancer (BCa) progression is driven by ongoing interactions between evolving tumor cells and the host immune system. Antitumor immunity is not the same across all BCa subtypes and depends on the quality, localization, and functional state of immune cells within the tumor microenvironment (TME). Highly immunogenic subtypes, such as triple-negative and HER2-positive (+) BCa, generally show stronger immune infiltration and inflammatory signaling, whereas estrogen receptor–positive tumors more often display immune-desert or immune-excluded phenotypes with limited immune cell infiltration and effector activity. Effective immune surveillance requires not only the presence of immune cells, but also their suitable spatial localization and functional capacity. Cytotoxic CD8+ T cells mediate tumor control when they infiltrate tumor areas, whereas stromal-related limitations or functional exhaustion reduces their efficacy. This dysfunction is reinforced by regulatory populations, including FoxP3+ regulatory T cells and CD163+ tumor-associated macrophages, which establish suppressive networks that inhibit effector responses. Within this framework, T-cell immunity is organized into distinct functional states, including stem-like progenitor exhausted T cells, which maintain their immune potential, and effector T cells responsible for cytotoxicity, which support local surveillance. Tertiary lymphoid structures further enhance coordinated immune activation by serving as intratumoral sites of antigen presentation and lymphocyte priming. Immune escape arises through T-cell exhaustion, impaired antigen presentation, tumor-intrinsic signaling changes, and stromal barriers that restrict infiltration. Collectively, these mechanisms generate a regulated, but often tumor-supporting immune environment. BCa progression therefore, reflects a balance between immune activation and suppression, governed by spatial organization and cellular stratification within the TME.