Tumor Microenvironment Modulation and Its Impact on Immunotherapy in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is known as a refractory and inoperable breast cancer subtype with the worst prognosis. The poor treatment response due to the lack of specific targetable receptors and its extremely invasive nature makes it a significant point of scientific interest. The tumor microenvironment (TME) in TNBC is a dynamic and diverse landscape composed of various cellular components involving immune cells (macrophages, dendritic cells, T lymphocytes, natural killer cells, and cytokines) and nonimmune cells (endothelial cells, cancer-associated fibroblasts, vascular smooth muscle cells, and extracellular matrix). TME functions paradoxically; being both an immunoreactive and an immunosuppressive factor, it contributes significantly to the immunomodulation and tumor development in TNBC. Novel immunotherapeutic strategies including adoptive cell transfer, cytokines, checkpoint inhibitors, monoclonal antibodies, vaccines, and TME modulation have been developed recently to reshape the TME and treat TNBC. Immunomodulatory medications can adjust the TME by suppressing angiogenesis, promoting infiltration of immune cells, blocking T regulatory cells, and boosting the efficacy of therapies. The intricate interplay between the immunological TME and cancer impacts the efficacy of immunotherapy and other anticancer treatments. This has revolutionized the landscape of cancer treatment for various solid tumor types, particularly TNBC. This chapter explores the implications of TME modulation for the immunotherapy of TNBC. Understanding the dynamics of the TME in TNBC is crucial for developing targeted immunotherapeutic strategies and advancing our knowledge of this aggressive breast cancer subtype.