ArticleJCI insight2019
Tumor cell oxidative metabolism as a barrier to PD-1 blockade immunotherapy in melanoma.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 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
148 citing papers in PubMed, 235 citations in OpenAlex.
- Purinergic activity of circulating extracellular vesicles associates with disease progression in melanoma.Oncoimmunology · 2026Article
- Body mass index and dyslipidemia influence responses to anti-PD-1 immunotherapy in colorectal cancer.Annals of medicine · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Integrated hypoxia and metabolic gene signature to predict clinical outcomes and therapeutic vulnerabilities in lung adenocarcinoma.Journal of thoracic disease · 2026Article
- A Hypoxia-Apoptosis Stress-Adaptation State Defines Immune-Low Melanoma and Predicts Metastatic Risk.Cancers · 2026Article
- Immunosuppressive Pathways in Cutaneous Melanoma: Functional Integration Between PD-1 and CD73 and Therapeutic Implications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Combination Immunotherapy as a Promising Strategy to Overcome Immunotherapy Resistance: From Emergence to Next-Generation Approaches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Uncovering the Intricate and Heterogeneous Cellular Microenvironment of Cutaneous Melanoma.Medicina (Kaunas, Lithuania) · 2026Review
- Loss of ten-eleven translocation 2 (TET2) facilitates aggressive behaviour in cutaneous melanoma by inducing peroxisome proliferator-activated receptor-γ coactivator 1α expression and oxidative phosphorylation.The British journal of dermatology · 2026Article
- Investigating the determinants of immunotherapy response in the primary tumour of clear cell renal cell carcinoma (RCC).BMJ oncology · 2026Article
- Review
- IL-15 Complexes Combined with PD-1 Blockade Affect Immune Cell Distribution, Localization, and Immune Signatures in Regressing Versus Non-Regressing Metastatic Breast Tumors.International journal of molecular sciences · 2025Article
- Intra-tumoral hypoxia promotes CD8Immunity · 2025Article
- Mitochondrial bioenergetics and networks in melanoma: an update.Apoptosis : an international journal on programmed cell death · 2025Review
- Regulatory T cells in the tumour microenvironment.Nature reviews. Cancer · 2025Review
- Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities.Journal of experimental & clinical cancer research : CR · 2025Review
- Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.Molecular cancer · 2025Review
- Persistent lineage plasticity driving lung cancer development and progression.Clinical and translational medicine · 2025Review
- Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinoma.Scientific reports · 2025Article
88 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
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The tumor microenvironment presents physical, immunologic, and metabolic barriers to durable immunotherapy responses. We have recently described roles for both T cell metabolic insufficiency as well as tumor hypoxia as inhibitory mechanisms that prevent T cell activity in murine tumors, but whether intratumoral T cell activity or response to immunotherapy varies between patients as a function of distinct metabolic profiles in tumor cells remains unclear. Here, we show that metabolic derangement can vary widely in both degree and type in patient-derived cell lines and in ex vivo analysis of patient samples, such that some cells demonstrate solely deregulated oxidative or glycolytic metabolism. Further, deregulated oxidative, but not glycolytic, metabolism was associated with increased generation of hypoxia upon implantation into immunodeficient animals. Generation of murine single-cell melanoma cell lines that lacked either oxidative or glycolytic metabolism showed that elevated tumor oxygen consumption was associated with increased T cell exhaustion and decreased immune activity. Moreover, melanoma lines lacking oxidative metabolism were solely responsive to anti-PD-1 therapy among those tested. Prospective analysis of patient sample immunotherapy revealed that oxidative, but not glycolytic, metabolism was associated with progression on PD-1 blockade. Our data highlight a role for oxygen as a crucial metabolite required for the tumor-infiltrating T cells to differentiate appropriately upon PD-1 blockade, and suggest that tumor oxidative metabolism may be a target to improve immunotherapeutic response.
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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.