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b-Catenin Drives Bu...
b-Catenin Drives Butyrophilin-like Molecule Loss and gd T-cell Exclusion in Colon Cancer
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- Suzuki, Toshiyasu (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland
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- Kilbey, Anna (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland
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- Casa-Rodriguez, Nuria (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland
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- Lawlor, Amy (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland
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- Georgakopoulou, Anastasia (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland
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- Hayman, Hannah (författare)
- Univ Glasgow, Scotland
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- Swe, Kyi Lai Yin (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland
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- Nordin, Anna (författare)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Wallenberg Centre for Molecular Medicine
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- Cantù, Claudio (författare)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Wallenberg Centre for Molecular Medicine
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- Vantourout, Pierre (författare)
- Kings Coll London, England; Francis Crick Inst, England
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- Ridgway, Rachel A. (författare)
- Canc Res UK Beatson Inst, Scotland
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- Byrne, Ryan M. (författare)
- Queens Univ, North Ireland
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- Chen, Lei (författare)
- Rutgers State Univ, NJ USA
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- Verzi, Michael P. (författare)
- Rutgers State Univ, NJ USA
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- Gay, David M. (författare)
- Canc Res UK Beatson Inst, Scotland
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- Vazquez, Ester Gil (författare)
- Univ Oxford, England
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- Belnoue-Davis, Hayley L. (författare)
- Univ Oxford, England
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- Gilroy, Kathryn (författare)
- Canc Res UK Beatson Inst, Scotland
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- Kostner, Anne Helene (författare)
- Southern Hosp Trust, Norway
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- Kersten, Christian (författare)
- Southern Hosp Trust, Norway; Akershus Univ Hosp, Norway
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- Thuwajit, Chanitra (författare)
- Mahidol Univ, Thailand
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- Andersen, Ditte K. (författare)
- BioClavis Ltd, Scotland
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- Wiesheu, Robert (författare)
- Univ Glasgow, Scotland
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- Jandke, Anett (författare)
- Francis Crick Inst, England
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- Blyth, Karen (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland
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- Roseweir, Antonia K. (författare)
- Univ Glasgow, Scotland
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- Leedham, Simon J. (författare)
- Univ Oxford, England
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- Dunne, Philip D. (författare)
- Canc Res UK Beatson Inst, Scotland; Queens Univ, North Ireland
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- Edwards, Joanne (författare)
- Univ Glasgow, Scotland
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- Hayday, Adrian (författare)
- Kings Coll London, England; Francis Crick Inst, England
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- Sansom, Owen J. (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland
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- Coffelt, Seth B. (författare)
- Canc Res UK Beatson Inst, Scotland; Univ Glasgow, Scotland; Canc Res UK Beatson Inst, Scotland
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(creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2023
- 2023
- Engelska.
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Ingår i: CANCER IMMUNOLOGY RESEARCH. - : AMER ASSOC CANCER RESEARCH. - 2326-6066. ; 11:8, s. 1137-1155
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Intraepithelial lymphocytes (IEL) expressing y8 T-cell receptors (y8TCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immu-nosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic y8IELs. In contrast with healthy intestinal or colonic tissue, we found that y8IELs were largely absent from the micro-environment of both mouse and human tumors, and that butyr-ophilin-like (BTNL) molecules, which can critically regulate y8IEL through direct y8TCR interactions, were also downregulated in tumors. We then demonstrated that 13-catenin activation through loss of Apc rapidly suppressed expression of the mRNA encoding the HNF4A and HNF4G transcription factors, preventing their binding to promoter regions of Btnl genes. Reexpression of BTNL1 and BTNL6 in cancer cells increased y8IEL survival and activation in coculture assays but failed to augment their cancer-killing ability in vitro or their recruitment to orthotopic tumors. However, inhibition of 13-catenin signaling via genetic deletion of Bcl9/Bcl9L in either Apc-deficient or mutant 13-catenin mouse models restored Hnf4a, Hnf4g, and Btnl gene expression and y8 T-cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts y8IEL immunosurveillance and furthers cancer progression.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- art (ämneskategori)
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Suzuki, Toshiyas ...
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Kilbey, Anna
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Casa-Rodriguez, ...
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Lawlor, Amy
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Georgakopoulou, ...
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Hayman, Hannah
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visa fler...
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Swe, Kyi Lai Yin
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Nordin, Anna
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Cantù, Claudio
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Vantourout, Pier ...
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Ridgway, Rachel ...
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Byrne, Ryan M.
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Chen, Lei
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Verzi, Michael P ...
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Gay, David M.
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Vazquez, Ester G ...
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Belnoue-Davis, H ...
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Gilroy, Kathryn
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Kostner, Anne He ...
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Kersten, Christi ...
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Thuwajit, Chanit ...
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Andersen, Ditte ...
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Wiesheu, Robert
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Jandke, Anett
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Blyth, Karen
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Roseweir, Antoni ...
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Leedham, Simon J ...
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Dunne, Philip D.
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Edwards, Joanne
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Hayday, Adrian
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Sansom, Owen J.
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Coffelt, Seth B.
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