Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Microenvironment and Immunology

ICOS-Ligand Expression on Plasmacytoid Dendritic Cells Supports Breast Cancer Progression by Promoting the Accumulation of Immunosuppressive CD4+ T Cells

Julien Faget, Nathalie Bendriss-Vermare, Michael Gobert, Isabelle Durand, Daniel Olive, Cathy Biota, Thomas Bachelot, Isabelle Treilleux, Sophie Goddard-Leon, Emilie Lavergne, Sylvie Chabaud, Jean Yves Blay, Christophe Caux and Christine Ménétrier-Caux
Julien Faget
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathalie Bendriss-Vermare
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Gobert
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabelle Durand
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel Olive
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cathy Biota
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Bachelot
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabelle Treilleux
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sophie Goddard-Leon
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emilie Lavergne
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sylvie Chabaud
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean Yves Blay
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christophe Caux
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christine Ménétrier-Caux
Authors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, FranceAuthors' Affiliations: Team 11, Cancer Research Center of Lyon, INSERM; Université Lyon, ISPB; Centre Léon Bérard; Centre Léon Bérard, BioPathology Department; Centre Léon Bérard, Medical Oncology Department; Centre Léon Bérard, Biostatistic Department, Lyon, France; and Inserm U891 Institut Paoli Calmettes Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/0008-5472.CAN-12-2409 Published December 2012
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Human breast tumors are infiltrated by memory CD4+ T cells along with increased numbers of regulatory T cells (Treg) and plasmacytoid dendritic cells (pDC) that facilitate immune escape and correlate with poor prognosis. Here, we report that inducible costimulatory molecule (ICOS), a T cell costimulatory molecule of the CTLA4/PD1/CD28 family, is expressed mostly by tumor-associated Treg in primary breast tumors. A large proportion of these ICOS+ Treg were Ki67+ and this evident proliferative expansion was found to rely on interactions with tumor-associated pDC. Indeed, tumor-associated Treg highly expanded in presence of pDC but failed to proliferate under CD3/CD28 signal. In vitro experiments revealed that the addition of a neutralizing anti-ICOS antibody blocked pDC-induced Treg expansion and interleukin-10 secretion by memory CD4+ T cells, establishing a pivotal role for ICOS in this process. Supporting these findings, the presence of ICOS+ cells in clinical specimens of breast cancer correlated with a poor prognosis. Together, our results highlight an important relationship between Treg and pDC in breast tumors, and show that ICOS/ICOS-L interaction is a central event in immunosuppression of tumor-associated memory CD4+ T cells. These findings strongly rationalize antibody-mediated ICOS blockade as a powerful clinical strategy to correct immune escape and promote therapeutic responses in breast cancer. Cancer Res; 72(23); 6130–41. ©2012 AACR.

Footnotes

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

  • Received June 19, 2012.
  • Revision received September 13, 2012.
  • Accepted September 13, 2012.
  • ©2012 American Association for Cancer Research.
View Full Text
PreviousNext
Back to top
Cancer Research: 72 (23)
December 2012
Volume 72, Issue 23
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by Author

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
ICOS-Ligand Expression on Plasmacytoid Dendritic Cells Supports Breast Cancer Progression by Promoting the Accumulation of Immunosuppressive CD4+ T Cells
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
ICOS-Ligand Expression on Plasmacytoid Dendritic Cells Supports Breast Cancer Progression by Promoting the Accumulation of Immunosuppressive CD4+ T Cells
Julien Faget, Nathalie Bendriss-Vermare, Michael Gobert, Isabelle Durand, Daniel Olive, Cathy Biota, Thomas Bachelot, Isabelle Treilleux, Sophie Goddard-Leon, Emilie Lavergne, Sylvie Chabaud, Jean Yves Blay, Christophe Caux and Christine Ménétrier-Caux
Cancer Res December 1 2012 (72) (23) 6130-6141; DOI: 10.1158/0008-5472.CAN-12-2409

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
ICOS-Ligand Expression on Plasmacytoid Dendritic Cells Supports Breast Cancer Progression by Promoting the Accumulation of Immunosuppressive CD4+ T Cells
Julien Faget, Nathalie Bendriss-Vermare, Michael Gobert, Isabelle Durand, Daniel Olive, Cathy Biota, Thomas Bachelot, Isabelle Treilleux, Sophie Goddard-Leon, Emilie Lavergne, Sylvie Chabaud, Jean Yves Blay, Christophe Caux and Christine Ménétrier-Caux
Cancer Res December 1 2012 (72) (23) 6130-6141; DOI: 10.1158/0008-5472.CAN-12-2409
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Grants Support
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • TLR4-Mediated Inflammation Promotes Cellular Transformation
  • CD103 Signaling in Human TRM Cells
  • Expansion of Neoclonotypes and Anti–PD-1 Clinical Efficiency
Show more Microenvironment and Immunology
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement