Role of Immune Checkpoints (PD-1, PDL1 and CTLA-4) In Triple-Negative Breast Cancer and Therapeutic Implications

Abstract

Triple-negative breast cancer (TNBC) is one of the most prominent types of breast cancer. It is a very aggressive subtype that is characterized by the absence of certain receptors which are expected on the surface of tumor cells. Limited treatment options and a poor prognosis, highlight an urgent need for continuous research and effective therapies. This paper reviews the role of immune checkpoints in TNBC with a focus on the probable system of immune evasion by tumor cells. It also provides a simple overview of the current state of immune checkpoint inhibitors (ICIs) as monotherapies, including anti-PD-1/PD-L1 (e.g., pembrolizumab, atezolizumab) and anti-CTLA-4 (e.g., ipilimumab) therapies, as well as their limitations in breast cancer treatment. This review is based on an extensive analysis of relevant scientific literature obtained from reputable peer-reviewed journals, databases, and reports. It synthesized current knowledge on the role of immune checkpoints in TNBC, including their mechanistic involvement in immune suppression and prognostic implications. Advanced studies in cancer immunotherapy have highlighted the potential of targeting immune checkpoints, such as PD-1/PD-L1 and CTLA-4, to overcome immune evasion in TNBC. These immune checkpoints play a pivotal role in shaping the tumor microenvironment (TME) by suppressing T-cell activation and promoting tumor immune tolerance. Combination therapies involving ICIs with chemotherapy, radiotherapy, or other immunomodulatory approaches are also examined, highlighting their synergistic potential. Clinical trials have demonstrated the efficacy of immune checkpoint inhibitors (ICIs), with pembrolizumab plus chemotherapy improving progression-free survival (PFS) in PD-L1+ metastatic TNBC. By optimizing immune-based strategies and overcoming resistance mechanisms, these advancements have the potential to improve survival rates and quality of life for TNBC patients. Furthermore, emerging therapeutic strategies, including dual checkpoint blockade, modulation of the TME, and neoantigen-based immunotherapies, are proposed as innovative avenues for enhancing immune response and overcoming resistance to current treatments.