The Role of Tumor Microenvironment in Triple-Negative Breast Cancer and Its Therapeutic Targeting

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by rapid proliferation and infiltration of immune cells into tumor microenvironment (TME). The treatment of TNBC still remains challenging due to the lack of expression of effective molecular targets pertaining to the tumor cell itself. In TNBC standard of care, therapies such as chemotherapy, together with recently introduced immunotherapy with checkpoint inhibitors, often do not result in durable clinical response. Therefore, better understanding of complex interactions between tumor cells, immune cells, and stromal cells mediated by multiple cytokines, chemokines, enzymes, and metabolites in TME is crucial for understanding the mechanisms that underlie tumor cell immune evasion strategies. The aim of this review is to give comprehensive overview of immune cell network and their interactions with cells in TME and possibilities for therapeutic targeting of TME in TNBC. We discuss cancer-associated fibroblasts (CAFs) as an important recently characterized player in TNBC with respect to their role in interactions with immune cells and their impact on tumor invasion. Based on the recently accumulated knowledge, therapies targeting immune suppressive mechanisms and CAF-related tumor-promoting mechanisms in TME hold great potential for clinical evaluation in TNBC. © 2025 by the authors.