Over the past decade, immune-checkpoint inhibitors (ICIs) have revolutionized cancer therapy by significantly improving treatment outcomes for certain patients. These inhibitors, which target immune checkpoints like CTLA-4 and PD1/PDL1, have transformed the field of oncology, leading to a more holistic approach in evaluating treatment efficacy and managing adverse events. The introduction of ICI therapy marked a turning point, reversing the previous state where immunotherapy was ineffective and toxic. Today, immunotherapy leads the field, with immunologists playing a major role in cancer research, as evidenced by the 2018 Nobel Prize in Medicine awarded to James Allison and Tasuku Honjo. ICIs have led to remarkable clinical progress, particularly in treating aggressive cancers like metastatic melanoma. They have also introduced new preclinical models and biomarkers, such as tumor-infiltrating T cells, PDL1 expression, and tumor mutational burden (TMB). TMB has become a key factor in predicting response to immunotherapy, with highly mutated tumors, such as those in smokers, responding better. This has led to the authorization of anti-PD1 drugs for cancers with high TMB, such as those with mismatch repair deficiency. ICIs have also changed the way clinical trials are evaluated, with new endpoints like restricted mean survival time being more suitable. Additionally, the adverse events associated with ICI are distinct from those of traditional therapies, often involving immune-mediated inflammation. These events require close collaboration between oncologists and specialists to manage effectively. While ICI has shown long-term remission in some patients, it is not a cure for all cancers. The future of ICI therapy depends on identifying biomarkers for efficacy and toxicity, optimizing treatment regimens, and exploring new combinations. Despite their success, ICI therapy remains a promising but complex area of cancer treatment.Over the past decade, immune-checkpoint inhibitors (ICIs) have revolutionized cancer therapy by significantly improving treatment outcomes for certain patients. These inhibitors, which target immune checkpoints like CTLA-4 and PD1/PDL1, have transformed the field of oncology, leading to a more holistic approach in evaluating treatment efficacy and managing adverse events. The introduction of ICI therapy marked a turning point, reversing the previous state where immunotherapy was ineffective and toxic. Today, immunotherapy leads the field, with immunologists playing a major role in cancer research, as evidenced by the 2018 Nobel Prize in Medicine awarded to James Allison and Tasuku Honjo. ICIs have led to remarkable clinical progress, particularly in treating aggressive cancers like metastatic melanoma. They have also introduced new preclinical models and biomarkers, such as tumor-infiltrating T cells, PDL1 expression, and tumor mutational burden (TMB). TMB has become a key factor in predicting response to immunotherapy, with highly mutated tumors, such as those in smokers, responding better. This has led to the authorization of anti-PD1 drugs for cancers with high TMB, such as those with mismatch repair deficiency. ICIs have also changed the way clinical trials are evaluated, with new endpoints like restricted mean survival time being more suitable. Additionally, the adverse events associated with ICI are distinct from those of traditional therapies, often involving immune-mediated inflammation. These events require close collaboration between oncologists and specialists to manage effectively. While ICI has shown long-term remission in some patients, it is not a cure for all cancers. The future of ICI therapy depends on identifying biomarkers for efficacy and toxicity, optimizing treatment regimens, and exploring new combinations. Despite their success, ICI therapy remains a promising but complex area of cancer treatment.