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

Primary Tumor Hypoxia Recruits CD11b+/Ly6Cmed/Ly6G+ Immune Suppressor Cells and Compromises NK Cell Cytotoxicity in the Premetastatic Niche

Jaclyn Sceneay, Melvyn T. Chow, Anna Chen, Heloise M. Halse, Christina S.F. Wong, Daniel M. Andrews, Erica K. Sloan, Belinda S. Parker, David D. Bowtell, Mark J. Smyth and Andreas Möller
Jaclyn Sceneay
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melvyn T. Chow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heloise M. Halse
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christina S.F. Wong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel M. Andrews
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erica K. Sloan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Belinda S. Parker
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David D. Bowtell
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark J. Smyth
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas Möller
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/0008-5472.CAN-11-3873
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Hypoxia within a tumor acts as a strong selective pressure that promotes angiogenesis, invasion, and metastatic spread. In this study, we used immune competent bone marrow chimeric mice and syngeneic orthotopic mammary cancer models to show that hypoxia in the primary tumor promotes premetastatic niche formation in secondary organs. Injection of mice with cell-free conditioned medium derived from hypoxic mammary tumor cells resulted in increased bone marrow–derived cell infiltration into the lung in the absence of a primary tumor and led to increased metastatic burden in mammary and melanoma experimental metastasis models. By characterizing the composition of infiltrating bone marrow–derived cells, we identified CD11b+/Ly6Cmed/Ly6G+ myeloid and CD3−/NK1.1+ immune cell lineages as key constituents of the premetastatic niche. Furthermore, the cytotoxicity of natural killer (NK) cells was significantly decreased, resulting in a reduced antitumor response that allowed metastasis formation in secondary organs to a similar extent as ablation of NK cells. In contrast, metastatic burden was decreased when active NK cells were present in premetastatic lungs. Together, our findings suggest that primary tumor hypoxia provides cytokines and growth factors capable of creating a premetastatic niche through recruitment of CD11b+/Ly6Cmed/Ly6G+ myeloid cells and a reduction in the cytotoxic effector functions of NK cell populations. Cancer Res; 1–6. ©2012 AACR.

Footnotes

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

  • Received November 30, 2011.
  • Revision received April 16, 2012.
  • Accepted May 19, 2012.
  • ©2012 American Association for Cancer Research.
Next
Back to top

Published OnlineFirst July 10, 2012
doi: 10.1158/0008-5472.CAN-11-3873

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.
Primary Tumor Hypoxia Recruits CD11b+/Ly6Cmed/Ly6G+ Immune Suppressor Cells and Compromises NK Cell Cytotoxicity in the Premetastatic Niche
(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
Primary Tumor Hypoxia Recruits CD11b+/Ly6Cmed/Ly6G+ Immune Suppressor Cells and Compromises NK Cell Cytotoxicity in the Premetastatic Niche
Jaclyn Sceneay, Melvyn T. Chow, Anna Chen, Heloise M. Halse, Christina S.F. Wong, Daniel M. Andrews, Erica K. Sloan, Belinda S. Parker, David D. Bowtell, Mark J. Smyth and Andreas Möller
Cancer Res July 10 2012 DOI: 10.1158/0008-5472.CAN-11-3873

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Primary Tumor Hypoxia Recruits CD11b+/Ly6Cmed/Ly6G+ Immune Suppressor Cells and Compromises NK Cell Cytotoxicity in the Premetastatic Niche
Jaclyn Sceneay, Melvyn T. Chow, Anna Chen, Heloise M. Halse, Christina S.F. Wong, Daniel M. Andrews, Erica K. Sloan, Belinda S. Parker, David D. Bowtell, Mark J. Smyth and Andreas Möller
Cancer Res July 10 2012 DOI: 10.1158/0008-5472.CAN-11-3873
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
  • 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