The online version of this article (doi:10.1007/s00262-014-1542-y) contains supplementary material, which is available to authorized users.
Immune responses wane during aging, posing challenges to the potential effectiveness of cancer immunotherapies. We previously demonstrated that in the context of a promising immunotherapeutic, OX40 agonist (αOX40), older animals exhibited impaired anti-tumor immune responses and diminished CD4 T cell effector differentiation. In this study, we hypothesized that 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 calorically 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 after challenging with either sarcoma or breast tumor cells followed by αOX40 treatment. Our results show that CR, but not RES, maintained OX40-mediated anti-tumor immunity. In addition, CR fully sustained antigen-specific CD4 T cell priming in aged hosts (12 months old), whereas tumor-specific CD8 T cell priming was not fully maintained compared to young reference animals (2 months old). Thus, CR appears to maintain immunological fitness of the CD4 T cell priming environment during aging, which is critical for optimal OX40-mediated responses.
Supplementary material 1 (PDF 450 kb)262_2014_1542_MOESM1_ESM.pdf
Effros RB, Svoboda K, Walford RL (1991) Influence of age and caloric restriction on macrophage IL-6 and TNF production. Lymphokine Cytokine Res 10:347–351 PubMed
Pahlavani MA (2004) Influence of caloric restriction on aging immune system. J Nutr Health Aging 8:38–47 PubMed
Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951 PubMed
Kjaergaard J, Tanaka J, Kim JA, Rothchild K, Weinberg A, Shu S (2000) Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res 60:5514–5521 PubMed
- Caloric restriction maintains OX40 agonist-mediated tumor immunity and CD4 T cell priming during aging
Andrew D. Weinberg
Carl E. Ruby
- Springer Berlin Heidelberg
Neu im Fachgebiet Onkologie
Mail Icon II