ArticleCell metabolism2016
Tumor-Induced IL-6 Reprograms Host Metabolism to Suppress Anti-tumor Immunity.
Article in Cell metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 2 of them syntheses that pooled it.
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Who cites it
254 citing papers in PubMed, 2 syntheses or guidelines pooled it, 351 citations in OpenAlex.
- Cancer cachexia reduces the efficacy of immune checkpoint inhibitors in cancer patients.Aging · 2024Pooled it
- Imaging-based adipose biomarkers for predicting clinical outcomes of cancer patients treated with immune checkpoint inhibitors: a systematic review.Frontiers in oncology · 2023Pooled it
- Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Adding anti-PD-1 antibody to definitive chemoradiotherapy in elderly patients with esophageal squamous cell carcinoma: higher intensity does not equate to better outcomes.Annals of medicine · 2026Article
- A health-system-scale, episode-resolved multimodal atlas of cancer cachexia.Nature medicine · 2026Article
- The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026Review
- Signaling Under Stress: Targeting the Glucocorticoid Receptor in Cancer.Cancer research · 2026Review
- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- Article
- Loss of cold shock domain-containing protein E1 (CSDE1) function enhances mRNA stability of interleukin-6 and promotes malignant transformation in endometrial cancer cells.Cell communication and signaling : CCS · 2026Article
- Article
- Cancer cachexia: A tumor-driven disorder of whole-body homeostasis.Cancer cell · 2026Review
- Anatomical dynamics define cancer cachexia subtypes and identify systemic inflammation as a marker of lethal wasting.medRxiv : the preprint server for health sciences · 2026Article
- Impact of baseline nutritional and inflammatory markers on safety and efficacy of immune checkpoint inhibitors in cancer patients: a retrospective, monocentric study.Discover oncology · 2026Article
- Hypoalbuminemia induces immunosuppression through disorder in macrophages and drives resistance to immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2026Article
- Identification of Hidden Cachexia Subgroup in PD-L1-High NSCLC: Comparative Analysis of the AWGC vs. Fearon Criteria.Journal of cachexia, sarcopenia and muscle · 2026Article
- Separating anorexia -dependent and -independent effects in cancer cachexia.bioRxiv : the preprint server for biology · 2026Article
- A Novel Mouse Model to Identify Antigen-Specific Immune Responses in Pancreatic Cancer Cachexia.Cancers · 2026Article
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Interleukin 6 Drives Durable T Cell-Mediated Immunity to Pancreatic Cancer.Cellular and molecular gastroenterology and hepatology · 2026Article
194 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
In patients with cancer, the wasting syndrome, cachexia, is associated with caloric deficiency. Here, we describe tumor-induced alterations of the host metabolic response to caloric deficiency that cause intratumoral immune suppression. In pre-cachectic mice with transplanted colorectal cancer or autochthonous pancreatic ductal adenocarcinoma (PDA), we find that IL-6 reduces the hepatic ketogenic potential through suppression of PPARalpha, the transcriptional master regulator of ketogenesis. When these mice are challenged with caloric deficiency, the resulting relative hypoketonemia triggers a marked rise in glucocorticoid levels. Multiple intratumoral immune pathways are suppressed by this hormonal stress response. Moreover, administering corticosterone to elevate plasma corticosterone to a level that is lower than that occurring in cachectic mice abolishes the response of mouse PDA to an immunotherapy that has advanced to clinical trials. Therefore, tumor-induced IL-6 impairs the ketogenic response to reduced caloric intake, resulting in a systemic metabolic stress response that blocks anti-cancer immunotherapy.
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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.