Correction of age-associated defects in dendritic cell functions enables CD4+ T cells to eradicate tumors in the elderly
Zhivaki, D.; Borriello, F.; Kennedy, S.; Evavold, C. L.; Bahleda, K. M.; Chapman, K. L.; Zanoni, I.; Kagan, J. C.
Show abstract
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.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4+ T cell response 96%
- Cellular selectivity of STING stimulation determines priming of tumor-specific T cell responses 96%
- Regulatory T cells restrain skin inflammation by modulating peripheral neuron activation 95%
Similar papers in this journal
- Metformin enhances anti-mycobacterial responses by educating immunometabolic circuits of CD8+ T cells 97%
- Recruited macrophages that colonise the post-inflammatory peritoneal niche convert into functionally divergent resident cells 96%
- T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling 96%
Similar papers in this journal
- Early and Delayed STAT1-Dependent Responses Drive Local Trained Immunity of Macrophages in the Spleen 96%
- Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2 96%
- Integration of IL-2 and IL-4 Signals Coordinates Divergent Regulatory T cell Responses and Drives Therapeutic Efficacy 95%
Similar papers in this journal
- Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy 96%
- Inflammatory cytokines mediate the induction of and awakening from metastatic dormancy 96%
- Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis 95%
Similar papers in this journal
- Interruption of thymic activity in adults improves responses to tumor immunotherapy 95%
- Interferon-sensitized hematopoietic progenitors dynamically alter organismal immunity 95%
- Mucosal vaccine adjuvant cyclic di-GMP differentiates lung moDCs into Bcl6+ and Bcl6- mature moDCs to induce lung memory CD4+ TH cells and lung TFH cells respectively 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.