Immune responses progressively wane during aging, posing significant challenges to the protection and treatment of cancer. We previously demonstrated that in the context of OX40 costimulation older animals exhibited impaired anti-tumor immune responses and diminished CD4 T cell effector differentiation. We hypothesized that anti-tumor immune responses could be maintained during aging through caloric restriction (CR) or dietary supplementation with resveratrol (RES), a CR mimetic. Mice were placed on either a restricted diet or a RES-formulated diet starting between 4 and 6 months of age and continued until mice reached 12 months of age. Tumor immune responses were assessed by challenging with either sarcoma or breast tumor cells followed by agonist OX40 treatment. Our results show CR, but not RES, maintained OX40-mediated anti-tumor immunity, during aging. In addition, CR maintained tumor-specific CD4 T cell activation in aged mice. This observed effect of CR on T cell activation, lead to an assessment of DCs. We found that the accumulation of an inflammatory DC subset (CD11c+CD11b+Ly6C+), critical for the activation of CD4 T cells, was significantly decreased in the LNs of older control mice compared to young mice. In contrast, CR aged mice had more inflammatory DCs in the priming LNs compared to aged controls. Thus, CR appears to maintain immunological fitness of a DC subset during aging that is critical for antigen-specific CD4 T cell activation and tumor immunity.
- Copyright © 2013 by The American Association of Immunologists, Inc.