ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 27 citations in OpenAlex.
- Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics.Molecular psychiatry · 2026Article
- NKT cells-a generalist in disease treatment and a new key to unlock immunotherapy.Immunotherapy · 2025Review
- Role of TSC1 in physiology and diseases.Molecular and cellular biochemistry · 2021Review
- Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.Nature communications · 2021Article
- Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.European journal of immunology · 2020Article
- Metabolic coordination of T cell quiescence and activation.Nature reviews. Immunology · 2020Review
- Differential Control ofFrontiers in immunology · 2019Article
- Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myeloma.Leukemia · 2017Article
- Article
- Alpha-Galactosylceramide/CD1d-Antibody Fusion Proteins Redirect Invariant Natural Killer T Cell Immunity to Solid Tumors and Promote Prolonged Therapeutic Responses.Frontiers in immunology · 2017Review
- Essential Role of mTORC1 in Self-Renewal of Murine Alveolar Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium.Scientific reports · 2016Article
- Article
- NK cell development requires Tsc1-dependent negative regulation of IL-15-triggered mTORC1 activation.Nature communications · 2016Article
- Id2 regulates hyporesponsive invariant natural killer T cells.Immunology and cell biology · 2016Article
- mTORC2 in Thymic Epithelial Cells Controls Thymopoiesis and T Cell Development.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- NKT cell subsets as key participants in liver physiology and pathology.Cellular & molecular immunology · 2016Review
- mTOR Regulation of Lymphoid Cells in Immunity to Pathogens.Frontiers in immunology · 2016Review
- Diacylglycerol Kinases in T Cell Tolerance and Effector Function.Frontiers in cell and developmental biology · 2016Review
- mTOR and its tight regulation for iNKT cell development and effector function.Molecular immunology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Development of effective immune therapies for cancer patients requires better understanding of hurdles that prevent the generation of effective antitumor immune responses. Administration of α-galactosylceramide (α-GalCer) in animals enhances antitumor immunity via activation of the invariant NKT (iNKT) cells. However, repeated injections of α-GalCer result in long-term unresponsiveness or anergy of iNKT cells, severely limiting its efficacy in tumor eradication. The mechanisms leading to iNKT cell anergy remain poorly understood. We report in this study that the tuberous sclerosis 1 (TSC1), a negative regulator of mTOR signaling, plays a crucial role in iNKT cell anergy. Deficiency of TSC1 in iNKT cells results in resistance to α-GalCer-induced anergy, manifested by increased expansion of and cytokine production by iNKT cells in response to secondary Ag stimulation. It is correlated with impaired upregulation of programmed death-1, Egr2, and Grail. Moreover, TSC1-deficient iNKT cells display enhanced antitumor immunity in a melanoma lung metastasis model. Our data suggest targeting TSC1/2 as a strategy for boosting antitumor immune therapy.
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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.