Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing the immune system's ability to recognize and attack tumor cells. ICIs target proteins such as PD-1, PD-L1, and CTLA-4, which regulate T cell activity. While these therapies have shown promise, resistance and tolerance remain significant challenges. Recent research has identified additional immune checkpoint targets, including TIGIT, TIM-3, LAG-3, VISTA, BTLA, and SIRPα, which are now being explored for their potential to improve treatment outcomes. PD-1/PD-L1 mAbs, such as nivolumab and pembrolizumab, have been approved for various cancers, including melanoma and non-small cell lung cancer (NSCLC). These mAbs work by blocking the interaction between PD-1 and its ligands, thereby restoring T cell function. Combination therapies with PD-1/PD-L1 mAbs and other agents, such as anti-angiogenic drugs or chemotherapy, have shown improved efficacy in treating advanced cancers. For example, the combination of pembrolizumab and axitinib has been effective in treating advanced renal cell carcinoma (RCC). Radiotherapy, when combined with immunotherapy, has shown potential in enhancing tumor immune responses. The abscopal effect, where radiation at one site reduces tumor growth in distant sites, is a promising area of research. Clinical trials have demonstrated that combining radiotherapy with PD-1 mAbs can improve outcomes in patients with locally advanced rectal cancer. Cell therapies, including CAR-T and TCR-T cell therapies, have also shown promise in cancer treatment. These therapies involve genetically modifying T cells to target tumor cells more effectively. CAR-T cell therapy has been particularly successful in treating certain hematologic malignancies, while TCR-T cell therapy is being explored for solid tumors. CTLA-4 mAbs, such as ipilimumab and tremelimumab, have been used in combination with PD-1 mAbs to enhance immune responses. The combination of nivolumab and ipilimumab has shown improved survival rates in patients with NSCLC. Emerging immune checkpoint inhibitors, such as LAG-3 and TIM-3 mAbs, are being investigated for their potential to improve treatment outcomes. These mAbs work by blocking the inhibitory signals that suppress T cell activity. Clinical trials have shown that combining LAG-3 and PD-1 mAbs can enhance immune responses and improve survival in patients with melanoma and other cancers. Overall, the development of new immune checkpoint inhibitors and combination therapies continues to advance cancer treatment, offering new hope for patients with difficult-to-treat cancers.Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing the immune system's ability to recognize and attack tumor cells. ICIs target proteins such as PD-1, PD-L1, and CTLA-4, which regulate T cell activity. While these therapies have shown promise, resistance and tolerance remain significant challenges. Recent research has identified additional immune checkpoint targets, including TIGIT, TIM-3, LAG-3, VISTA, BTLA, and SIRPα, which are now being explored for their potential to improve treatment outcomes. PD-1/PD-L1 mAbs, such as nivolumab and pembrolizumab, have been approved for various cancers, including melanoma and non-small cell lung cancer (NSCLC). These mAbs work by blocking the interaction between PD-1 and its ligands, thereby restoring T cell function. Combination therapies with PD-1/PD-L1 mAbs and other agents, such as anti-angiogenic drugs or chemotherapy, have shown improved efficacy in treating advanced cancers. For example, the combination of pembrolizumab and axitinib has been effective in treating advanced renal cell carcinoma (RCC). Radiotherapy, when combined with immunotherapy, has shown potential in enhancing tumor immune responses. The abscopal effect, where radiation at one site reduces tumor growth in distant sites, is a promising area of research. Clinical trials have demonstrated that combining radiotherapy with PD-1 mAbs can improve outcomes in patients with locally advanced rectal cancer. Cell therapies, including CAR-T and TCR-T cell therapies, have also shown promise in cancer treatment. These therapies involve genetically modifying T cells to target tumor cells more effectively. CAR-T cell therapy has been particularly successful in treating certain hematologic malignancies, while TCR-T cell therapy is being explored for solid tumors. CTLA-4 mAbs, such as ipilimumab and tremelimumab, have been used in combination with PD-1 mAbs to enhance immune responses. The combination of nivolumab and ipilimumab has shown improved survival rates in patients with NSCLC. Emerging immune checkpoint inhibitors, such as LAG-3 and TIM-3 mAbs, are being investigated for their potential to improve treatment outcomes. These mAbs work by blocking the inhibitory signals that suppress T cell activity. Clinical trials have shown that combining LAG-3 and PD-1 mAbs can enhance immune responses and improve survival in patients with melanoma and other cancers. Overall, the development of new immune checkpoint inhibitors and combination therapies continues to advance cancer treatment, offering new hope for patients with difficult-to-treat cancers.