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

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • 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
  • My Cart

Search

  • Advanced search
Cancer Immunology Research
Cancer Immunology Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Research Article

Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy

Lindsey M. Kuehm, Niloufar Khojandi, Alexander Piening, Lauryn E. Klevorn, Simone C. Geraud, Nicole R. McLaughlin, Kristine Griffett, Thomas P. Burris, Kelly D. Pyles, Afton M. Nelson, Mary L. Preuss, Kevin A. Bockerstett, Maureen J. Donlin, Kyle S. McCommis, Richard J. DiPaolo and Ryan M. Teague
Lindsey M. Kuehm
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Niloufar Khojandi
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander Piening
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexander Piening
Lauryn E. Klevorn
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simone C. Geraud
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicole R. McLaughlin
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicole R. McLaughlin
Kristine Griffett
2Saint Louis University School of Medicine, Pharmacological and Physiological Sciences, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kristine Griffett
Thomas P. Burris
2Saint Louis University School of Medicine, Pharmacological and Physiological Sciences, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kelly D. Pyles
3Saint Louis University School of Medicine, Biochemistry and Molecular Biology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kelly D. Pyles
Afton M. Nelson
4Webster University, Department of Biological Sciences, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Afton M. Nelson
Mary L. Preuss
4Webster University, Department of Biological Sciences, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin A. Bockerstett
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maureen J. Donlin
3Saint Louis University School of Medicine, Biochemistry and Molecular Biology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyle S. McCommis
3Saint Louis University School of Medicine, Biochemistry and Molecular Biology, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kyle S. McCommis
Richard J. DiPaolo
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
5Alvin J. Siteman NCI Comprehensive Cancer Center, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryan M. Teague
1Saint Louis University School of Medicine, Molecular Microbiology and Immunology, St. Louis, Missouri.
5Alvin J. Siteman NCI Comprehensive Cancer Center, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ryan.teague@health.slu.edu
DOI: 10.1158/2326-6066.CIR-20-0396
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Checkpoint blockade immunotherapy relies on the empowerment of the immune system to fight cancer. Why some patients fail to achieve durable clinical responses is not well understood, but unique individual factors such as diet, obesity, and related metabolic syndrome could play a role. The link between obesity and patient outcomes remains controversial and has been mired by conflicting reports and limited mechanistic insight. We addressed this in a C57BL/6 mouse model of diet-induced obesity using a Western diet high in both fats and sugars. Obese mice bearing B16 melanoma or MC38 carcinoma tumors had impaired immune responses to immunotherapy and a reduced capacity to control tumor progression. Unexpectedly, these compromised therapeutic outcomes were independent of body mass and, instead, were directly attributed to dietary fructose. Melanoma tumors in mice on the high-fructose diet were resistant to immunotherapy and showed increased expression of the cytoprotective enzyme heme oxygenase-1 (HO-1). This increase in HO-1 protein was recapitulated in human A375 melanoma cells exposed to fructose in culture. Induced expression of HO-1 shielded tumor cells from immune-mediated killing and was critical for resistance to checkpoint blockade immunotherapy, which could be overcome in vivo using a small-molecule inhibitor of HO-1. This study reveals dietary fructose as a driver of tumor immune evasion, identifying HO-1 expression as a mechanism of resistance and a promising molecular target for combination cancer immunotherapy.

Footnotes

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

  • Cancer Immunol Res 2020;XX:XX–XX

  • Received May 12, 2020.
  • Revision received August 3, 2020.
  • Accepted October 1, 2020.
  • Published first October 6, 2020.
  • ©2020 American Association for Cancer Research.

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

This OnlineFirst version was published on December 16, 2020
doi: 10.1158/2326-6066.CIR-20-0396

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

Thank you for sharing this Cancer Immunology 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.
Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy
(Your Name) has forwarded a page to you from Cancer Immunology Research
(Your Name) thought you would be interested in this article in Cancer Immunology Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy
Lindsey M. Kuehm, Niloufar Khojandi, Alexander Piening, Lauryn E. Klevorn, Simone C. Geraud, Nicole R. McLaughlin, Kristine Griffett, Thomas P. Burris, Kelly D. Pyles, Afton M. Nelson, Mary L. Preuss, Kevin A. Bockerstett, Maureen J. Donlin, Kyle S. McCommis, Richard J. DiPaolo and Ryan M. Teague
Cancer Immunol Res December 16 2020 DOI: 10.1158/2326-6066.CIR-20-0396

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy
Lindsey M. Kuehm, Niloufar Khojandi, Alexander Piening, Lauryn E. Klevorn, Simone C. Geraud, Nicole R. McLaughlin, Kristine Griffett, Thomas P. Burris, Kelly D. Pyles, Afton M. Nelson, Mary L. Preuss, Kevin A. Bockerstett, Maureen J. Donlin, Kyle S. McCommis, Richard J. DiPaolo and Ryan M. Teague
Cancer Immunol Res December 16 2020 DOI: 10.1158/2326-6066.CIR-20-0396
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

  • Nutlin-3a: An Immune-Checkpoint Activator for NK Cells in Neuroblastoma
  • Notch-regulated DCs Limit Inflammation and Carcinogenesis
  • Machine learning-based prognostic marker of HCC
Show more Research Article
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Cancer Immunology Essentials

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Immunology Research

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

Copyright © 2021 by the American Association for Cancer Research.

Cancer Immunology Research
eISSN: 2326-6074
ISSN: 2326-6066

Advertisement