Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

SIMPLE SUMMARY: The tumor microenvironment (TME) is a complicated network composed of various cells, signaling molecules, and extra cellular matrix. TME plays a crucial role in triple negative breast cancer (TNBC) immunomodulation and tumor progression, paradoxically, acting as an immunosuppressive as well as immunoreactive factor. Research regarding tumor immune microenvironment has contributed to a better understanding of TNBC subtype classification. Shall we treat patients precisely according to specific subtype classification? Moving beyond traditional chemotherapy, multiple clinical trials have recently implied the potential benefits of immunotherapy combined with chemotherapy. In this review, we aimed to elucidate the paradoxical role of TME in TNBC immunomodulation, summarize the subtype classification methods for TNBC, and explore the synergistic mechanism of chemotherapy plus immunotherapy. Our study may provide a new direction for the development of combined treatment strategies for TNBC. ABSTRACT: Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.