ArticleCancer & metabolism2022
Isotope tracing reveals distinct substrate preference in murine melanoma subtypes with differing anti-tumor immunity.
Article in Cancer & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Anti-PD1-IL18 immunoconjugate promotes effector T cell-mediated antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- Metabolic inflexibility promotes mitochondrial health during liver regeneration.Science (New York, N.Y.) · 2024Article
- Stable Isotope Tracing Analysis in Cancer Research: Advancements and Challenges in Identifying Dysregulated Cancer Metabolism and Treatment Strategies.Metabolites · 2024Review
- A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.Journal of experimental & clinical cancer research : CR · 2024Review
- Thiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma.American journal of physiology. Endocrinology and metabolism · 2024Article
- Metabolic underpinnings of cancer-related fatigue.American journal of physiology. Endocrinology and metabolism · 2024Review
- Metabolic Profiling to Assess Response to Targeted and Immune Therapy in Melanoma.International journal of molecular sciences · 2024Review
- Multifaceted effects of obesity on cancer immunotherapies: Bridging preclinical models and clinical data.Seminars in cancer biology · 2023Review
- Dichloroacetate as a novel pharmaceutical treatment for cancer-related fatigue in melanoma.American journal of physiology. Endocrinology and metabolism · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundResearch about tumor "metabolic flexibility"-the ability of cells to toggle between preferred nutrients depending on the metabolic context-has largely focused on obesity-associated cancers. However, increasing evidence for a key role for nutrient competition in the tumor microenvironment, as well as for substrate regulation of immune function, suggests that substrate metabolism deserves reconsideration in immunogenic tumors that are not strongly associated with obesity.
methodsWe compare two murine models: immunologically cold YUMM1.7 and immunologically-hot YUMMER1.7. We utilize stable isotope and radioisotope tracer-based metabolic flux studies as well as gas and liquid chromatography-based metabolomics analyses to comprehensively probe substrate preference in YUMM1.7 and YUMMER1.7 cells, with a subset of studies on the impact of available metabolites across a panel of five additional melanoma cell lines. We analyze bulk RNA-seq data and identify increased expression of amino acid and glucose metabolism genes in YUMMER1.7. Finally, we analyze melanoma patient RNA-seq data to identify potential prognostic predictors rooted in metabolism.
resultsWe demonstrate using stable isotope tracer-based metabolic flux studies as well as gas and liquid chromatography-based metabolomics that immunologically-hot melanoma utilizes more glutamine than immunologically-cold melanoma in vivo and in vitro. Analyses of human melanoma RNA-seq data demonstrate that glutamine transporter and other anaplerotic gene expression positively correlates with lymphocyte infiltration and function.
conclusionsHere, we highlight the importance of understanding metabolism in non-obesity-associated cancers, such as melanoma. This work advances the understanding of the correlation between metabolism and immunogenicity in the tumor microenvironment and provides evidence supporting metabolic gene expression as potential prognostic factors of melanoma progression and may inform investigations of adjunctive metabolic therapy in melanoma.
trial registrationDeidentified data from The Cancer Genome Atlas were analyzed.
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