Breaking Barriers: The Promise and Challenges of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with pronounced immunogenicity, exhibiting rapid proliferation and immune cell infiltration into the tumor microenvironment. TNBC’s heterogeneity poses challenges to immunological treatments, inducing resistance mechanisms in the tumor microenvironment. Therapeutic modalities, including immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4, are explored in preclinical and clinical trials. Promising results emerge from combining ICIs with anti-TGF-β and VISTA, hindering TNBC tumor growth. TNBC cells employ complex evasion strategies involving interactions with stromal and immune cells, suppressing immune recognition through various cytokines, chemokines, and metabolites. The recent focus on unraveling humoral and cellular components aims to disrupt cancer crosstalk within the tumor microenvironment. This review identifies TNBC’s latest resistance mechanisms, exploring potential targets for clinical trials to overcome immune checkpoint resistance and enhance patient survival rates.

Role of microRNAs in triple‑negative breast cancer and new therapeutic concepts (Review)

“…TGF-β is known to reprogram the tumor microenvironment in TNBC; it suppresses the immune system by increasing collagen production in cancer-associated fibroblasts ( 31 ). The TGF-β pathway has different roles in different stages of tumors.…”