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Mitigating Age-Related Immune Dysfunction Heightens the Efficacy of Tumor Immunotherapy in Aged Mice.
- Source :
-
Cancer Research . Apr2012, Vol. 72 Issue 8, p2089-2099. 2p. - Publication Year :
- 2012
-
Abstract
- Although cancer tends to affect the elderly, most preclinical studies are carried out in young subjects. In this study, we developed a melanoma- specific cancer immunotherapy that shows efficacy in aged but not young hosts by mitigating age- specific tumor-associated immune dysfunction. Both young and aged CD4þCD25hi regulatory T cells (Treg) exhibited equivalent in vitro T-cell suppression and tumor-associated augmentation in numbers. However, denileukin diftitox (DT)- mediated Treg depletion improved tumor-specific immunity and was clinically effective only in young mice. DT-mediated Treg depletion significantly increased myeloid-derived suppressor cell (MDSC) numbers in aged but not young mice, and MDSC depletion improved tumor-specific immunity and reduced tumor growth in aged mice. Combining Treg depletion with anti-Gr-1 antibody was immunolog-ically and clinically more efficacious than anti-Gr-1 antibody alone in aged B16-bearing mice, similar to Treg depletion alone in young mice. In contrast, DT increased MDSCs in young and aged mice following MC-38 tumor challenge, although effects were greater in aged mice. Anti-Gr-1 boosted DT effects in young but not aged mice. Aged antitumor immune effector cells are therefore competent to combat tumor when underlying tumor-associated immune dysfunction is appropriately mitigated, but this dysfunction varies with tumor, thus also varying responses to immunotherapy. By tailoring immunotherapy to account for age-related tumor-associated immune dysfunctions, cancer immunotherapy for aged patients with specific tumors can be remarkably improved. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00085472
- Volume :
- 72
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 77325346
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-11-3019