Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

OX40 Agonist Tumor Immunotherapy Does Not Impact Regulatory T Cell Suppressive Function

Fanny Polesso, Minhaz Sarker, Andrew D. Weinberg, Susan E. Murray and Amy E. Moran
J Immunol August 21, 2019, ji1900696; DOI: https://doi.org/10.4049/jimmunol.1900696
Fanny Polesso
*Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minhaz Sarker
†Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Minhaz Sarker
Andrew D. Weinberg
‡Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, OR 97213; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan E. Murray
†Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239;
§Biology Department, University of Portland, Portland, OR 97203
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amy E. Moran
*Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Amy E. Moran
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Key Points

  • Anti-OX40 treatment does not impair TIL Treg suppressive function.

  • OX40 ligation enhances Treg and Tconv proliferation through Tconv cell IL-2 secretion.

  • TIL Tregs proliferate and produce Th1 cytokines after anti-OX40 treatment.

Abstract

OX40 is a costimulatory molecule from the TNFR family. In mice, it is expressed on Foxp3+ regulatory T cells (Tregs) constitutively and on conventional CD4 (Tconv) and CD8 T cells after Ag encounter. OX40 agonists are in clinical development to enhance antitumor immune responses, and one proposed mechanism of action is loss of Treg suppressive function. Studies have postulated that agonist OX40 therapy can impair Treg suppressive function. Using tools developed since the initial studies were published, we evaluated a direct effect of OX40 agonism on Treg function. We conclude that OX40 agonist Abs do not intrinsically impair Treg function but rather enhance Tconv cell IL-2 production, increasing Treg and Tconv cell proliferation. OX40-stimulated Tregs retain suppressive function, but also gain IFN-γ, TNF-α, and granzyme B expression. These data help resolve mechanistic questions regarding OX40 agonist immunotherapy and thus are relevant to developing combination therapies that target distinct T cell functions.

Footnotes

  • This work was supported in part by American Cancer Society Postdoctoral Fellow Grant PF-14-053-01 and National Institutes of Health Grant T32AI078903, and an OHSU Foundation grant (to A.E.M.). A.D.W. was funded by National Institutes of Health Grant 5R01CA102577, a sponsored research agreement with MedImmune, and the Providence Medical Foundation. S.E.M. is supported by the Medical Research Foundation of Oregon and a grant from the M.J. Murdock Charitable Trust (NS-201812034).

  • The online version of this article contains supplemental material.

  • Received June 24, 2019.
  • Accepted July 22, 2019.
  • Copyright © 2019 by The American Association of Immunologists, Inc.
PreviousNext
Back to top

In this issue

The Journal of Immunology: 208 (10)
The Journal of Immunology
Vol. 208, Issue 10
15 May 2022
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Advertising (PDF)
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
OX40 Agonist Tumor Immunotherapy Does Not Impact Regulatory T Cell Suppressive Function
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OX40 Agonist Tumor Immunotherapy Does Not Impact Regulatory T Cell Suppressive Function
Fanny Polesso, Minhaz Sarker, Andrew D. Weinberg, Susan E. Murray, Amy E. Moran
The Journal of Immunology August 21, 2019, ji1900696; DOI: 10.4049/jimmunol.1900696

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
OX40 Agonist Tumor Immunotherapy Does Not Impact Regulatory T Cell Suppressive Function
Fanny Polesso, Minhaz Sarker, Andrew D. Weinberg, Susan E. Murray, Amy E. Moran
The Journal of Immunology August 21, 2019, ji1900696; DOI: 10.4049/jimmunol.1900696
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CXCL13 as a Novel Immune Checkpoint for Regulatory B Cells and Its Role in Tumor Metastasis
  • IL-27 Induces CCL5 Production by T Lymphocytes, Which Contributes to Antitumor Activity
  • Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125
Show more TUMOR IMMUNOLOGY

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • FAR 889
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2022 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606