Correction of age-associated defects in dendritic cell functions enables CD4+T cells to eradicate tumors in the elderly

Defective host defenses later in life are associated with changes in immune system activity. The means to correct immune defects to ensure immunity in the elderly are undefined. In this study, we found that CD8+T cells, which are necessary for anti-tumor immunity in young mice, are not required to eradicate the same cancers later in life. Rather, CD4+T cells drive anti-tumor immunity in elderly mice. The generation of anti-tumor CD4+T cells requires multiple dendritic cell (DC) activities that are elicited by immune agonists known as hyperactivators, but not by adjuvants that model those used clinically. DC hyperactivators correct age-associated defects in DC migration and T cell co-stimulation while enabling NLRP3 inflammasome activities within living cells. These combined activities enable DCs to induce TH1-skewed T cells that persist into old age and eliminate implantable tumors. These results raise the possibility of correcting age-associated immune defects through DC manipulation. 8 weeks or 92 weeks old mice were immunized with either PBS or OVA+LPS+PGPC. Mice received two boost injections every 7 days. 21 days post immunization, spleen samples were subjected to CD3e T cell enrichment to achieve highly pure (>85%) of CD3+ T cells. We then generated scRNA-seq data from splenic T cells using the NovaSeqX platform to explore the transcriptomic differences between the age groups.