ArticleThe Journal of experimental medicine2013
Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
103 citing papers in PubMed.
- Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy.Nature communications · 2026Article
- Senescent macrophages in tumor: phenotypes, roles, and interventions.Cell death & disease · 2025Review
- Effects of aging on anticancer therapy in murine cancer models.Cancer metastasis reviews · 2025Review
- Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges.Journal of hematology & oncology · 2025Review
- Restoring resident tissue macrophages to combat aging and cancer.Nature aging · 2025Review
- Involvement of TGF-β, mTOR, and inflammatory mediators in aging alterations during myxomatous mitral valve disease in a canine model.GeroScience · 2025Review
- Weight Loss Reverses the Effects of Aging and Obesity on Mammary Tumor Immunosuppression and Progression.Cancer prevention research (Philadelphia, Pa.) · 2025Article
- Preclinical models in the study of lymph node metastasis.Journal of Zhejiang University. Science. B · 2025Review
- Facts and Hopes of CD40 Agonists in Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Article
- Proceedings of the National Cancer Institute Workshop on combining immunotherapy with radiotherapy: challenges and opportunities for clinical translation.The Lancet. Oncology · 2025Article
- Healthy and premature aging of monocytes and macrophages.Frontiers in immunology · 2025Review
- Multifaceted Aspects of Dysfunctional Myelopoiesis in Cancer and Therapeutic Perspectives with Focus on HCC.Biomolecules · 2024Review
- Older adults with cancer and common comorbidities-challenges and opportunities in improving their cancer treatment outcomes.Journal of the National Cancer Institute · 2024Article
- Review
- The immunobiology of SARS-CoV-2 infection and vaccine responses: potential influences of cross-reactive memory responses and aging on efficacy and off-target effects.Frontiers in immunology · 2024Review
- Adipose tissue-derived extracellular vesicles from obese mice suppressed splenocyte-mediated pancreatic cancer cell death.Food & nutrition research · 2024Article
- Macrophages in Lung Repair and Fibrosis.Results and problems in cell differentiation · 2024Review
- Considerations and Approaches for Cancer Immunotherapy in the Aging Host.Cancer immunology research · 2023Review
- Multifaceted effects of obesity on cancer immunotherapies: Bridging preclinical models and clinical data.Seminars in cancer biology · 2023Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors.
Funding
Abstract
Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice.
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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.