ArticleCommunications biology2020
Absence of central tolerance in Aire-deficient mice synergizes with immune-checkpoint inhibition to enhance antitumor responses.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Pooled it
- Mechanism and intervention strategy of thymus atrophy in cancer immunotherapy.American journal of cancer research · 2026Review
- Transplantation of the MSLN-deficient Thymus Generates MSLN Epitope Reactive T Cells to Attenuate Tumor Progression.Cancer science · 2025Article
- Immunotherapy in thymic epithelial tumors: an attractive dilemma.Investigational new drugs · 2025Review
- RANK/RANKL Signaling Pathway in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- Transcript splicing optimizes the thymic self-antigen repertoire to suppress autoimmunity.The Journal of clinical investigation · 2024Article
- PRMT5: splicing up tolerance.The Journal of clinical investigation · 2024Article
- Thymic Mimetic Cells: Ontogeny as Immunology.Annual review of cell and developmental biology · 2024Review
- Immunotherapy for Thymomas and Thymic Carcinomas: Current Status and Future Directions.Cancers · 2024Review
- CTLA-4 on thymic epithelial cells complements Aire for T cell central tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients.Frontiers in immunology · 2022Article
- The role of immunotherapy for management of advanced thymic epithelial tumors: a narrative review.Mediastinum (Hong Kong, China) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endogenous anti-tumor responses are limited in part by the absence of tumor-reactive T cells, an inevitable consequence of thymic central tolerance mechanisms ensuring prevention of autoimmunity. Here we show that tumor rejection induced by immune checkpoint blockade is significantly enhanced in Aire-deficient mice, the epitome of central tolerance breakdown. The observed synergy in tumor rejection extended to different tumor models, was accompanied by increased numbers of activated T cells expressing high levels of Gzma, Gzmb, Perforin, Cxcr3, and increased intratumoural levels of Cxcl9 and Cxcl10 compared to wild-type mice. Consistent with Aire's central role in T cell repertoire selection, single cell TCR sequencing unveiled expansion of several clones with high tumor reactivity. The data suggest that breakdown in central tolerance synergizes with immune checkpoint blockade in enhancing anti-tumor immunity and may serve as a model to unmask novel anti-tumor therapies including anti-tumor TCRs, normally purged during central tolerance.
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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.