Role of immune checkpoint inhibitors in breast cancer and hematological malignancies

Cancer is a multifaceted and heterogeneous disease characterized by uncontrolled growth, evasion of immune surveillance, and resistance to conventional therapies. The immune system plays a crucial role in tumor surveillance. However, tumors exploit immune checkpoint pathways to inhibit T cell activation and evade immune destruction. Immune checkpoint inhibitors (ICIs) have markedly improved outcomes in certain cancers by restoring T cell function and enhancing anti-tumor immunity. Despite these advances, the presence of immune resistance mechanisms contributes to variability in responses and ongoing challenges in overcoming resistance. Triple-negative breast cancer (TNBC), compared to other breast cancer (BC) subtypes, exhibits higher immunogenicity, but its anti-tumor immunity is profoundly suppressed by immune checkpoint molecules, creating a paradoxical scenario of “high immunogenic potential yet restrained by inhibitory signals”. Consequently, TNBC has become a significant target for ICI therapy. However, response rates vary among BC subtypes, with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) BC demonstrating lower immunogenicity. Hematological malignancies, including leukemia, lymphoma, and multiple myeloma, also exhibit distinct immune checkpoint dynamics, influencing their responsiveness to ICIs. This review comprehensively examines the mechanisms of immune checkpoint regulation, their role in cancer immune evasion, and the clinical applications of ICIs in both solid and hematological malignancies. It further discusses emerging strategies to counteract ICI resistance, such as dual checkpoint blockade, tumor microenvironment modulation, metabolic targeting, and epigenetic reprogramming. An enhanced understanding of immune checkpoint biology is essential for optimizing immunotherapy strategies and improving patient outcomes. The literature selection for this study was guided by relevance to the research topic, focusing on peer-reviewed articles, monographs, and conference proceedings published between 2010 and 2025, sourced from databases like PubMed and Google Scholar.