Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high immunogenicity and specific immune signatures. Although these molecular features including elevated tumor-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) expression provide a strong rationale for immunotherapy, clinical response remains limited due to multiple mechanisms of immune escape. This review summarizes current and emerging immunotherapeutic strategies in TNBC, including immune checkpoint inhibitors (PDL-1 and cytotoxic T-lymphocyte-associated protein 4 (CTL-4) blockade), adoptive cell therapy (ACT) (chimeric antigen receptor T-cell therapy (CAR-T) and TIL therapy), oncolytic virotherapy, and antibody-based approaches. We also discuss the mechanisms of resistance including DNA damage response alterations, anti-apoptotic signaling, and tumor microenvironment-mediated resistance. Finally, we highlight rational combination strategies, immunotherapy with chemotherapy, targeted therapy, or additional immunotherapies that aim to enhance response to immunotherapy. Ongoing advances in immunotherapy hold significant potential to improve outcomes for patients with TNBC.
Alharbi et al. (2026) studied this question.