The study investigates the impact of aging on the tumor microenvironment (TME) and its effects on CD8+ T cell function in cancer. Key findings include: 1. **Aging and Tumor Growth**: Aging is associated with increased tumor growth and reduced CD8+ T cell infiltration and function. Transfer of young T cells into aged mice does not restore tumor control due to rapid T cell dysfunction. 2. **New Tumor-Infiltrating dysfunctional (T_TAD) Cell State**: The aged TME induces a novel, age-associated dysfunctional (T_TAD) cell state in CD8+ T cells, distinct from canonical T cell exhaustion. This state is functionally, transcriptionally, and epigenetically distinct from exhausted T cells. 3. **Cell-Extrinsic Signals in the Aged TME**: Altered natural killer (NK) cell–dendritic cell–CD8+ T cell cross-talk in aged tumors impairs T cell priming by conventional type 1 dendritic cells (cDC1s) and promotes T_TAD cell formation. Aged mice are unable to benefit from therapeutic mRNA vaccination due to these defects. 4. **Myeloid-Targeted Therapy**: Reinvigorating cDC1s through myeloid-targeted immunotherapies, such as CD40 agonism, can improve tumor control and enhance CD8+ T cell immunity in aged mice by restoring cDC1 function and improving T cell priming. 5. **Clinical Implications**: The presence of T_TAD cells is associated with poor tumor control in older individuals with cancer, suggesting that targeted adjuvant therapies to recruit more cDC1s and boost CD8+ T cell function may be necessary to improve immunotherapy outcomes in this population. Overall, the study highlights the importance of understanding the complex interplay between aging, the TME, and T cell dysfunction in cancer immunotherapy.The study investigates the impact of aging on the tumor microenvironment (TME) and its effects on CD8+ T cell function in cancer. Key findings include: 1. **Aging and Tumor Growth**: Aging is associated with increased tumor growth and reduced CD8+ T cell infiltration and function. Transfer of young T cells into aged mice does not restore tumor control due to rapid T cell dysfunction. 2. **New Tumor-Infiltrating dysfunctional (T_TAD) Cell State**: The aged TME induces a novel, age-associated dysfunctional (T_TAD) cell state in CD8+ T cells, distinct from canonical T cell exhaustion. This state is functionally, transcriptionally, and epigenetically distinct from exhausted T cells. 3. **Cell-Extrinsic Signals in the Aged TME**: Altered natural killer (NK) cell–dendritic cell–CD8+ T cell cross-talk in aged tumors impairs T cell priming by conventional type 1 dendritic cells (cDC1s) and promotes T_TAD cell formation. Aged mice are unable to benefit from therapeutic mRNA vaccination due to these defects. 4. **Myeloid-Targeted Therapy**: Reinvigorating cDC1s through myeloid-targeted immunotherapies, such as CD40 agonism, can improve tumor control and enhance CD8+ T cell immunity in aged mice by restoring cDC1 function and improving T cell priming. 5. **Clinical Implications**: The presence of T_TAD cells is associated with poor tumor control in older individuals with cancer, suggesting that targeted adjuvant therapies to recruit more cDC1s and boost CD8+ T cell function may be necessary to improve immunotherapy outcomes in this population. Overall, the study highlights the importance of understanding the complex interplay between aging, the TME, and T cell dysfunction in cancer immunotherapy.