ArticleCancer research2012
Mitigating age-related immune dysfunction heightens the efficacy of tumor immunotherapy in aged mice.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Cellular Senescence and Immunosenescence in Melanoma: Insights From the Tumor Microenvironment.Cancer medicine · 2025Pooled it
- Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8Molecular therapy. Nucleic acids · 2026Article
- Aging-Driven Immunosuppression: The Role of Tregs in the Ovarian Tumor Microenvironment.Aging cell · 2026Article
- Emerging Nanoplatforms are Effective Against Tumor Hypoxia.International journal of nanomedicine · 2026Review
- Anti-PD-L2 immunotherapy is efficacious against melanoma in aged hosts through IL-17 and IFNγ signalling.Nature communications · 2025Article
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- Age-associated nicotinamide adenine dinucleotide decline drives CAR-T cell failure.Nature cancer · 2025Article
- Effects of aging on anticancer therapy in murine cancer models.Cancer metastasis reviews · 2025Review
- Development of therapeutic cancer vaccines based on cancer immunity cycle.Frontiers of medicine · 2025Review
- An in-depth understanding of the role and mechanisms of T cells in immune organ aging and age-related diseases.Science China. Life sciences · 2025Review
- The crosstalk between senescence, tumor, and immunity: molecular mechanism and therapeutic opportunities.MedComm · 2025Review
- Review
- Second-generation checkpoint inhibitors and Treg depletion synergize with a mouse cancer vaccine in accordance with tumor microenvironment characterization.Journal for immunotherapy of cancer · 2024Article
- Accumulation of immune-suppressive CD4 + T cells in aging - tempering inflammaging at the expense of immunity.Seminars in immunology · 2023Review
- Considerations and Approaches for Cancer Immunotherapy in the Aging Host.Cancer immunology research · 2023Review
- Age-associated changes in the gut microbiome impact efficacy of tumor immunomodulatory treatments.Experimental gerontology · 2023Article
- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
- Age-associated remodeling of T cell immunity and metabolism.Cell metabolism · 2023Review
- Phototheranostics of Splenic Myeloid-Derived Suppressor Cells and Its Impact on Spleen Metabolism in Tumor-Bearing Mice.Cancers · 2022Article
- Aging-associated and CD4 T-cell-dependent ectopic CXCL13 activation predisposes to anti-PD-1 therapy-induced adverse events.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
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 CD4(+)CD25(hi) 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 immunologically 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.