ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Stimulation of the glucocorticoid-induced TNF receptor family-related receptor on CD8 T cells induces protective and high-avidity T cell responses to tumor-specific antigens.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Development of a fully human anti-GITR antibody with potent antitumor activity using H2L2 mice.FEBS open bio · 2022Article
- Current strategies in engaging oncolytic viruses with antitumor immunity.Molecular therapy oncolytics · 2021Review
- Determinants of Resistance to Checkpoint Inhibitors.International journal of molecular sciences · 2020Review
- Peritumoral administration of DRibbles-pulsed antigen-presenting cells enhances the antitumor efficacy of anti-GITR and anti-PD-1 antibodies via an antigen presenting independent mechanism.Journal for immunotherapy of cancer · 2019Article
- Costimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes.Nature communications · 2019Article
- NEDD4 Negatively Regulates GITR via Ubiquitination in Immune Microenvironment of Melanoma.OncoTargets and therapy · 2019Article
- The promise and challenges of immune agonist antibody development in cancer.Nature reviews. Drug discovery · 2018Review
- Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8Nature communications · 2017Article
- GITR ligand fusion protein agonist enhances the tumor antigen-specific CD8 T-cell response and leads to long-lasting memory.Journal for immunotherapy of cancer · 2017Article
- Combination strategies to enhance the potency of monocyte-derived dendritic cell-based cancer vaccines.Immunotherapy · 2016Review
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- Enhanced CD8 T cell responses through GITR-mediated costimulation resolve chronic viral infection.PLoS pathogens · 2015Article
- T cell avidity and tumor immunity: problems and solutions.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2014Article
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- Article
- Modulation of GITR for cancer immunotherapy.Current opinion in immunology · 2012Review
- CD8+ T cells: GITR matters.TheScientificWorldJournal · 2012Review
- Murine B cell development and antibody responses to model antigens are not impaired in the absence of the TNF receptor GITR.PloS one · 2012Article
- Targeting regulatory T cells in cancer.Cancer research · 2011Review
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Treatment of tumor-bearing mice with a stimulatory Ab to glucocorticoid-induced TNFR family-related receptor (GITR) has previously been shown to elicit protective T cell responses against poorly immunogenic tumors. However, the role of GITR stimulation on CD8 T cells and the nature of tumor rejection Ags have yet to be determined. In this study, we show that a stimulatory mAb to GITR (clone DTA-1) acts directly on CD8 T cells, but not on CD4(+)CD25(+) regulatory T (T(reg)) cells, in B16 tumor-bearing mice to induce concomitant immunity against secondary B16 tumors, as well as protective memory following surgical excision of the primary tumor. Melanoma growth itself induced GITR expression on tumor-specific CD8 T cells, providing a mechanism whereby these cells may respond to stimulatory anti-GITR. Unexpectedly, in contrast to T(reg) cell depletion therapy with anti-CD4, GITR stimulation induced very weak CD8 T cell responses to melanocyte differentiation Ags expressed by the tumor, and did not induce autoimmune vitiligo. Accordingly, GITR-stimulated hosts that were primed with B16 melanoma rejected B16, but not the unrelated JBRH melanoma, indicating that tumor rejection Ags are tumor-specific rather than shared. In support of this, we show that GITR stimulation induces CD8 T cell responses to a tumor-specific Ag, and that these responses are of higher functional avidity compared with those induced by T(reg) cell depletion. We conclude that stimulation of GITR on effector CD8 T cells results in high-avidity T cell responses to tumor-specific Ags, thereby inducing potent antitumor immunity in the absence of autoimmunity.
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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.