Abstract

Immune checkpoint inhibitors (ICIs) targeting PD-1 (programmed cell death-1) and CTLA-4 (cytotoxic T-lymphocyte antigen-4) have revolutionized cancer immunotherapy, providing durable responses in various cancers, including melanoma, lung cancer, and renal cell carcinoma. These inhibitors function by blocking immune checkpoints, enhancing T-cell activity against tumor cells. While PD-1 and CTLA-4 inhibitors have shown promising results, challenges remain regarding their efficacy, resistance mechanisms, and patient selection. The combination of PD-1 and CTLA-4 inhibitors has demonstrated synergistic effects, improving therapeutic outcomes compared to monotherapies. However, immunerelated adverse events (irAEs) are a significant concern. Ongoing research is focused on optimizing dosing strategies, exploring biomarkers for patient selection, and addressing mechanisms of resistance. This review discusses the current landscape of PD-1 and CTLA-4 inhibition in cancer therapy, evaluates emerging therapies and combination strategies, and explores future directions for improving outcomes and mitigating side effects.