Cytotoxic CD8+ T cells are crucial in the immune response against cancer and are central to current cancer immunotherapies. These cells, part of the adaptive immune system, are the most effective effectors in anticancer immunity. Immune-checkpoint inhibitors target inhibitory receptors to restore T-cell function, while adoptive cell transfer uses genetically modified CD8+ T cells with chimeric antigen receptors (CARs) to enhance their activity. New generations of CAR T-cells are being tested in clinical trials, and combination therapies are being explored to improve outcomes and reduce side effects. CD8+ T cells recognize antigens presented by MHC molecules and require co-stimulatory signals, such as CD28, for full activation. The TCR complex, including CD3 and CD8, plays a key role in signal transduction. CD8 enhances TCR-MHC complex stability and sensitivity. T-cell activation involves mechanical forces that facilitate target cell killing through granzymes, perforin, and Fas ligand. Cancer cells can evade immune detection by downregulating MHC expression and secreting enzymes that degrade perforin. T-cell exhaustion, characterized by reduced function and expression of inhibitory receptors like PD-1 and CTLA-4, is a major challenge in immunotherapy. Immune-checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, have significantly improved cancer treatment outcomes, particularly in melanoma and other malignancies. CAR T-cell therapy involves engineering T cells to recognize tumor antigens, with first-generation CARs being less effective than later generations that include co-stimulatory domains. CAR T-cells have shown success in treating certain leukemias and lymphomas, but challenges include cytokine release syndrome and toxicity. Advances in gene editing and synthetic receptors aim to improve safety and efficacy. The tumor microenvironment (TME) plays a critical role in immune evasion, with factors like hypoxia, fibrosis, and immunosuppressive cells contributing to resistance. Tumor-infiltrating CD8+ T cells are associated with better responses to immunotherapy, while cold tumors with low T-cell infiltration are less responsive. Strategies to enhance T-cell infiltration and function, such as targeting PD-L1 and improving TME conditions, are being explored. Immune-checkpoint inhibitors and CAR T-cell therapies are transforming cancer treatment, with ongoing research into combination therapies and novel approaches to overcome resistance. The future of cancer immunotherapy lies in personalized, multi-modal strategies that enhance immune responses while minimizing toxicity.Cytotoxic CD8+ T cells are crucial in the immune response against cancer and are central to current cancer immunotherapies. These cells, part of the adaptive immune system, are the most effective effectors in anticancer immunity. Immune-checkpoint inhibitors target inhibitory receptors to restore T-cell function, while adoptive cell transfer uses genetically modified CD8+ T cells with chimeric antigen receptors (CARs) to enhance their activity. New generations of CAR T-cells are being tested in clinical trials, and combination therapies are being explored to improve outcomes and reduce side effects. CD8+ T cells recognize antigens presented by MHC molecules and require co-stimulatory signals, such as CD28, for full activation. The TCR complex, including CD3 and CD8, plays a key role in signal transduction. CD8 enhances TCR-MHC complex stability and sensitivity. T-cell activation involves mechanical forces that facilitate target cell killing through granzymes, perforin, and Fas ligand. Cancer cells can evade immune detection by downregulating MHC expression and secreting enzymes that degrade perforin. T-cell exhaustion, characterized by reduced function and expression of inhibitory receptors like PD-1 and CTLA-4, is a major challenge in immunotherapy. Immune-checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, have significantly improved cancer treatment outcomes, particularly in melanoma and other malignancies. CAR T-cell therapy involves engineering T cells to recognize tumor antigens, with first-generation CARs being less effective than later generations that include co-stimulatory domains. CAR T-cells have shown success in treating certain leukemias and lymphomas, but challenges include cytokine release syndrome and toxicity. Advances in gene editing and synthetic receptors aim to improve safety and efficacy. The tumor microenvironment (TME) plays a critical role in immune evasion, with factors like hypoxia, fibrosis, and immunosuppressive cells contributing to resistance. Tumor-infiltrating CD8+ T cells are associated with better responses to immunotherapy, while cold tumors with low T-cell infiltration are less responsive. Strategies to enhance T-cell infiltration and function, such as targeting PD-L1 and improving TME conditions, are being explored. Immune-checkpoint inhibitors and CAR T-cell therapies are transforming cancer treatment, with ongoing research into combination therapies and novel approaches to overcome resistance. The future of cancer immunotherapy lies in personalized, multi-modal strategies that enhance immune responses while minimizing toxicity.