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Quiescent Tissue Stem Cells Evade Immune Surveillance
Open accessAbstract
Stem cells are critical for the maintenance of many tissues, but whether their integrity is maintained in the face of immunity is unclear. Here we found that cycling epithelial stem cells, including Lgr5+ intestinal stem cells, as well as ovary and mammary stem cells, were eliminated by activated T cells, but quiescent stem cells in the hair follicle and muscle were resistant to T cell killing. Immune evasion was an intrinsic property of the quiescent stem cells resulting from systemic downregulation of the antigen presentation machinery, including MHC class I and TAP proteins, and is mediated by the transactivator NLRC5. This process was reversed upon stem cell entry into the cell cycle. These studies identify a link between stem cell quiescence, antigen presentation, and immune evasion. As cancer-initiating cells can derive from stem cells, these findings may help explain how the earliest cancer cells evade immune surveillance.
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“Jedi T cells enable GFP to be used as a model antigen that can be easily detected (Agudo et al., 2018).”
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Metadata
- Authors
- Agudo, J., Park, E. S., Rose, S. A., Alibo, E., Sweeney, R., Dhainaut, M., Kobayashi, K. S., Sachidanandam, R., Baccarini, A., Merad, M., & Brown, B. D.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Hokkaido University (JP)
- Tisch Cancer Institute (US)
- Corresponding author
- Brown, Brian D.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 48
- Issue
- 2
- Pages
- 271-285.e5
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC5824652
- OpenAlex
- W2788425782
- Cited by
- 244
- References
- 59
- Citations by year
- 2026: 18 · 2025: 35 · 2024: 32 · 2023: 30 · 2022: 31 · 2021: 30 · 2020: 30 · 2019: 26 · 2018: 12
- FWCI
- 10.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01AI104848, R01AI113221, R21OD020185, R01DK106593)
- Robin Chemers Neustein Award
- Juvenile Diabetes Research Foundation (JDRF) (3-2013-92)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- quiescent stem cells, immune evasion, antigen presentation, MHC class I, TAP, NLRC5, T cell-mediated killing, epithelial stem cells, intestinal stem cells, Lgr5, hair follicle stem cells, muscle stem cells, mammary stem cells, stem cell quiescence, tumor surveillance, cancer stem cells
- MeSH terms
- Animals, Immunologic Surveillance, Killer Cells, Natural, Mice, Inbred C57BL, Muscles, Stem Cells, Antigen Presentation, Hair Follicle, Tumor Escape, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, Mice, Immune Evasion
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