ArticleJournal for immunotherapy of cancer2019
Metabolic stress in cancer cells induces immune escape through a PI3K-dependent blockade of IFNγ receptor signaling.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 82 citations in OpenAlex.
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Chirality-Encoded Biomaterials Regulate Local and Systemic Immune Responses in Transplantation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- From PIK3CA Mutations to Rational PI3K Inhibition for the Treatment of Colorectal Cancer.Molecular diagnosis & therapy · 2026Review
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- One-carbon metabolism in cancer immunity: T-cell fitness, epigenetic programming, and therapeutic opportunities.Frontiers in immunology · 2026Review
- A comprehensive review of mechanisms underlying resistance to immune checkpoint inhibitors.Frontiers in immunology · 2026Review
- Mapping real-time metabolic kinetics of expanded CAR T cells using hyperpolarizedScientific reports · 2025Article
- EZH2 loss during metabolic stress drives restoration of MHC class I machinery in melanoma.iScience · 2025Article
- Combining Apatinib and Oxaliplatin Remodels the Immunosuppressive Tumor Microenvironment and Sensitizes Desert-Type Gastric Cancer to Immunotherapy.Cancer research · 2025Article
- Comparison of clinicopathological parameters with the presence of Epstein-Barr virus and the absence of DNA mismatch repair proteins in gastric adenocarcinomas.Asian biomedicine : research, reviews and news · 2025Article
- Immune checkpoint blockade for cancer therapy: current progress and perspectives.Journal of Zhejiang University. Science. B · 2025Review
- Persist or resist: Immune checkpoint inhibitors in EGFR-mutated NSCLC.Cancer science · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities.Journal of translational medicine · 2025Review
- Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.The Journal of experimental medicine · 2025Article
- Cold and hot tumors: from molecular mechanisms to targeted therapy.Signal transduction and targeted therapy · 2024Review
- Immunosurveillance encounters cancer metabolism.EMBO reports · 2024Review
- Increased peritoneal TGF-β1 is associated with ascites-induced NK-cell dysfunction and reduced survival in high-grade epithelial ovarian cancer.Frontiers in immunology · 2024Article
- Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects.Molecular cancer · 2023Review
- Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance.Cancer research · 2023Article
1 more citing papers are in PubMed but not listed here.
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7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundT-cell mediated immunotherapy brought clinical success for many cancer patients. Nonetheless, downregulation of MHC class I antigen presentation, frequently occurring in solid cancers, limits the efficacy of these therapies. Unraveling the mechanisms underlying this type of immune escape is therefore of great importance. We here investigated the immunological effects of metabolic stress in cancer cells as a result of nutrient deprivation.
methodsTC1 and B16F10 tumor cell lines were cultured under oxygen- and glucose-deprivation conditions that mimicked the tumor microenvironment of solid tumors. Presentation of peptide antigens by MHC class I molecules was measured by flow cytometry and via activation of tumor-specific CD8 T cell clones. The proficiency of the IFNy-STAT1 pathway was investigated by Western blots on phosphorylated proteins, transfection of constitutive active STAT1 constructs and qPCR of downstream targets. Kinase inhibitors for PI3K were used to examine its role in IFNy receptor signal transduction.
resultsCombination of oxygen- and glucose-deprivation resulted in decreased presentation of MHC class I antigens on cancer cells, even in the presence of the stimulatory cytokine IFNy. This unresponsiveness to IFNy was the result of failure to phosphorylate the signal transducer STAT1. Forced expression of constitutive active STAT1 fully rescued the MHC class I presentation. Furthermore, oxygen- and glucose-deprivation increased PI3K activity in tumor cells. Pharmacological inhibition of this pathway not only restored signal transduction through IFNy-STAT1 but also improved MHC class I presentation. Importantly, PI3K inhibitors also rendered tumor cells sensitive for recognition by CD8 T cells in culture conditions of metabolic stress.
conclusionsThese data revealed a strong impact of metabolic stress on the presentation of tumor antigens by MHC class I and suggest that this type of tumor escape takes place at hypoxic areas even during times of active T cell immunity and IFNy release.
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