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Cancer Immunology Research
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The E3 Ubiquitin Ligase Asb2α in T Helper 2 Cells Negatively Regulates Antitumor Immunity in Colorectal Cancer

Camille A. Spinner, Isabelle Lamsoul, Arnaud Métais, Chanaëlle Febrissy, Christel Moog-Lutz and Pierre G. Lutz
Camille A. Spinner
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
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Isabelle Lamsoul
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
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  • ORCID record for Isabelle Lamsoul
  • For correspondence: Pierre.Lutz@ipbs.fr Isabelle.Lamsoul@ipbs.fr
Arnaud Métais
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
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Chanaëlle Febrissy
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
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Christel Moog-Lutz
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
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Pierre G. Lutz
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
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  • ORCID record for Pierre G. Lutz
  • For correspondence: Pierre.Lutz@ipbs.fr Isabelle.Lamsoul@ipbs.fr
DOI: 10.1158/2326-6066.CIR-18-0562 Published August 2019
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Abstract

The escape of cancer cells from host immunosurveillance involves a shift in immune responses, including an imbalance in Th1 and Th2 cells. A Th1-dominated immune response predicts positive outcomes in colorectal cancer. The E3 ubiquitin ligase, Asb2α, is expressed in Th2 cells, but its roles in T-cell maturation and cancer are unclear. We provide evidence that the Th2 master regulator, Gata3, induces Asb2. Loss of Asb2 did not affect Th differentiation ex vivo, but reduced IL4 production from Th2 cells. We found that high ASB2 expression was associated with poor outcome in colorectal cancer. Loss of Asb2 from hematopoietic cells promoted a Th1 response and attenuated colitis-associated tumorigenesis in mice. Diminished Th2 function correlated with increased IFNγ production and an enhanced type 1 antitumor immune response in Asb2-deficient mice. Our work suggests that Asb2α promotes a Th2 phenotype in vivo, which in turn is associated with tumor progression in a mouse model of colitis.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Cancer Immunol Res 2019;7:1332–44

  • Received August 17, 2018.
  • Revision received January 14, 2019.
  • Accepted June 5, 2019.
  • Published first June 7, 2019.
  • ©2019 American Association for Cancer Research.
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Cancer Immunology Research: 7 (8)
August 2019
Volume 7, Issue 8
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The E3 Ubiquitin Ligase Asb2α in T Helper 2 Cells Negatively Regulates Antitumor Immunity in Colorectal Cancer
Camille A. Spinner, Isabelle Lamsoul, Arnaud Métais, Chanaëlle Febrissy, Christel Moog-Lutz and Pierre G. Lutz
Cancer Immunol Res August 1 2019 (7) (8) 1332-1344; DOI: 10.1158/2326-6066.CIR-18-0562

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The E3 Ubiquitin Ligase Asb2α in T Helper 2 Cells Negatively Regulates Antitumor Immunity in Colorectal Cancer
Camille A. Spinner, Isabelle Lamsoul, Arnaud Métais, Chanaëlle Febrissy, Christel Moog-Lutz and Pierre G. Lutz
Cancer Immunol Res August 1 2019 (7) (8) 1332-1344; DOI: 10.1158/2326-6066.CIR-18-0562
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