| First Author | Zhivaki D | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 15 | Pages | 3888-3903.e18 |
| PubMed ID | 38870946 | Mgi Jnum | J:351006 |
| Mgi Id | MGI:7665132 | Doi | 10.1016/j.cell.2024.05.026 |
| Citation | Zhivaki D, et al. (2024) Correction of age-associated defects in dendritic cells enables CD4(+) T cells to eradicate tumors. Cell |
| abstractText | Defective host defenses later in life are associated with changes in immune cell activities, suggesting that age-specific considerations are needed in immunotherapy approaches. In this study, we found that PD-1 and CTLA4-based cancer immunotherapies are unable to eradicate tumors in elderly mice. This defect in anti-tumor activity correlated with two known age-associated immune defects: diminished abundance of systemic naive CD8(+) T cells and weak migratory activities of dendritic cells (DCs). We identified a vaccine adjuvant, referred to as a DC hyperactivator, which corrects DC migratory defects in the elderly. Vaccines containing tumor antigens and DC hyperactivators induced T helper type 1 (TH1) CD4(+) T cells with cytolytic activity that drive anti-tumor immunity in elderly mice. When administered early in life, DC hyperactivators were the only adjuvant identified that elicited anti-tumor CD4(+) T cells that persisted into old age. These results raise the possibility of correcting age-associated immune defects through DC manipulation. |
