ArticleThe Journal of experimental medicine2020
Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 216 papers.
What it found
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Who cites it
216 citing papers in PubMed, 313 citations in OpenAlex.
- Rosuvastatin enhances the efficacy of venetoclax-azacitidine in older acute myeloid leukemia patients via reducing T-cell exhaustion.Cancer immunology, immunotherapy : CII · 2026Trial
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- Sprayable hydrogel loaded with engineered fusion cellular vesicles for cancer recurrence suppression.Journal of nanobiotechnology · 2026Article
- Coixenolide Enhances Antitumor Immunity of Cytotoxic CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Menaquinone-4 protects CD8Science China. Life sciences · 2026Article
- Metabolic Bottlenecks and Opportunities: Reshaping the Tumor Microenvironment for Cancer Immunotherapy.Cells · 2026Review
- The interplay between lipid metabolism, cancer progression and anti-cancer immunity.Experimental & molecular medicine · 2026Review
- CXCR2-mediated metabolic interaction between prostate cancer cells and the immunosuppressive tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- ASB2 inhibits lipid accumulation to promote ILC1 homeostatic fitness and anti-tumor immunity in the mouse liver.Nature communications · 2026Article
- Ascites-derived lipid barrier at the T cell synapse.Nature metabolism · 2026Article
- Lipids in ovarian cancer ascites impair T cell activation by disrupting TCR dynamics.Nature metabolism · 2026Article
- Targeting DGAT1 reprograms lipid landscape and restores CD8⁺ T cell immunity in pancreatic cancer.Nature communications · 2026Article
- USP1-mediated lipophagy-lipogenesis axis drives cholangiocarcinoma progression and immune evasion.Journal for immunotherapy of cancer · 2026Article
- T-Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan-Cancer Characteristics, and Therapeutic Interventions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Short-, medium-, versus long-chain fatty acids: mechanisms of immunomodulation and disease pathogenesis.Cellular & molecular immunology · 2026Review
- Multifunctional Role of Mitochondrial Fatty Acid Oxidation in Cancer Immunotherapy and Aging.Cancer science · 2026Review
- From guardians to traitors: molecular mechanisms of tumor-induced T cell betrayal.Molecular cancer · 2026Review
- Patient-derived organotypic tumor spheroids as a functional platform for predicting immunotherapeutic responses and guiding precision treatment for hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
156 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 6 institutions in 3 countries.
Funding
Abstract
CD8+ T cells are master effectors of antitumor immunity, and their presence at tumor sites correlates with favorable outcomes. However, metabolic constraints imposed by the tumor microenvironment (TME) can dampen their ability to control tumor progression. We describe lipid accumulation in the TME areas of pancreatic ductal adenocarcinoma (PDA) populated by CD8+ T cells infiltrating both murine and human tumors. In this lipid-rich but otherwise nutrient-poor TME, access to using lipid metabolism becomes particularly valuable for sustaining cell functions. Here, we found that intrapancreatic CD8+ T cells progressively accumulate specific long-chain fatty acids (LCFAs), which, rather than provide a fuel source, impair their mitochondrial function and trigger major transcriptional reprogramming of pathways involved in lipid metabolism, with the subsequent reduction of fatty acid catabolism. In particular, intrapancreatic CD8+ T cells specifically exhibit down-regulation of the very-long-chain acyl-CoA dehydrogenase (VLCAD) enzyme, which exacerbates accumulation of LCFAs and very-long-chain fatty acids (VLCFAs) that mediate lipotoxicity. Metabolic reprogramming of tumor-specific T cells through enforced expression of ACADVL enabled enhanced intratumoral T cell survival and persistence in an engineered mouse model of PDA, overcoming one of the major hurdles to immunotherapy for PDA.
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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.