From cold to hot tumors: feasibility of applying therapeutic insights to TNBC.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is characterized by the absence of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). Due to its immunosuppressive tumour microenvironment (TME) and low immune cell infiltration, TNBC typically exhibits poor responsiveness to immunotherapy. Recent relevant research has focused on using strategies to convert cold tumors into hot tumors to increase tumor immunogenicity and improve treatment efficacy. This review aims to summarize the biological characteristics of both cold and hot tumors and explore the mechanisms underlying the transformation from cold to hot tumors. Key strategies include modulation of the TME, enhancement of immune cell infiltration, and regulation of the inflammatory responses. Additionally, the roles of immune checkpoint inhibitors (ICIs), cytokine therapy, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines in reprogramming the TME are discussed. Further, the emerging combination strategies, such as the integration of ICIs with chemotherapy, radiotherapy, and targeted therapies, have been evaluated for their potential to increase TNBC immunogenicity. Current preclinical and clinical evidence suggests that reprogramming the TME through targeted interventions significantly increases immune cell infiltration and antigen presentation, thereby improving the immunotherapy efficacy in TNBC. The combinations of ICIs with chemotherapy and radiotherapy have shown promise in shifting the TME toward an immunoresponsive state. Moreover, advances in the CAR-T-cell therapy, cytokine therapy, and cancer vaccines have offered novel approaches for overcoming immune resistance in TNBC. In conclusion, transforming cold tumors into hot tumors represents a promising therapeutic strategy for TNBC. Future research should focus on optimizing the treatment combinations, refining therapeutic timing and dosage, and integrating precision medicine approaches to achieve maximized clinical benefits. A deeper understanding of TME modulation and immune resistance mechanisms would facilitate the development of novel immunotherapeutic strategies to improve the survival outcomes and quality of life in TNBC patients.