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

Priority Brief

Activation of CD8+ T Cells Contributes to Antitumor Effects of CDK4/6 Inhibitors plus MEK Inhibitors

Jessica L.F. Teh, Dan A. Erkes, Phil F. Cheng, Manoela Tiago, Nicole A. Wilski, Conroy O. Field, Inna Chervoneva, Mitch P. Levesque, Xiaowei Xu, Reinhard Dummer and Andrew E. Aplin
Jessica L.F. Teh
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jessica L.F. Teh
Dan A. Erkes
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Phil F. Cheng
2Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Phil F. Cheng
Manoela Tiago
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicole A. Wilski
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicole A. Wilski
Conroy O. Field
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Inna Chervoneva
3Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania.
4Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitch P. Levesque
2Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaowei Xu
5Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Xiaowei Xu
Reinhard Dummer
2Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew E. Aplin
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
4Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andrew E. Aplin
  • For correspondence: Andrew.Aplin@Jefferson.edu
DOI: 10.1158/2326-6066.CIR-19-0743 Published September 2020
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below.

Abstract

Concurrent MEK and CDK4/6 inhibition shows promise in clinical trials for patients with advanced-stage mutant BRAF/NRAS solid tumors. The effects of CDK4/6 inhibitor (CDK4/6i) in combination with BRAF/MEK-targeting agents on the tumor immune microenvironment are unclear, especially in melanoma, for which immune checkpoint inhibitors are effective in approximately 50% of patients. Here, we show that patients progressing on CDK4/6i/MEK pathway inhibitor combinations exhibit T-cell exclusion. We found that MEK and CDK4/6 targeting was more effective at delaying regrowth of mutant BRAF melanoma in immunocompetent versus immune-deficient mice. Although MEK inhibitor (MEKi) treatment increased tumor immunogenicity and intratumoral recruitment of CD8+ T cells, the main effect of CDK4/6i alone and in combination with MEKi was increased expression of CD137L, a T-cell costimulatory molecule on immune cells. Depletion of CD8+ T cells or blockade of the CD137 ligand–receptor interaction reduced time to regrowth of melanomas in the context of treatment with CDK4/6i plus MEKi treatment in vivo. Together, our data outline an antitumor immune-based mechanism and show the efficacy of targeting both the MEK pathway and CDK4/6.

Footnotes

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

  • Cancer Immunol Res 2020;8:1114–21

  • Received October 2, 2019.
  • Revision received March 19, 2020.
  • Accepted June 26, 2020.
  • Published first July 13, 2020.
  • ©2020 American Association for Cancer Research.
View Full Text

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
Cancer Immunology Research: 8 (9)
September 2020
Volume 8, Issue 9
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

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 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.
Activation of CD8+ T Cells Contributes to Antitumor Effects of CDK4/6 Inhibitors plus MEK Inhibitors
(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
Activation of CD8+ T Cells Contributes to Antitumor Effects of CDK4/6 Inhibitors plus MEK Inhibitors
Jessica L.F. Teh, Dan A. Erkes, Phil F. Cheng, Manoela Tiago, Nicole A. Wilski, Conroy O. Field, Inna Chervoneva, Mitch P. Levesque, Xiaowei Xu, Reinhard Dummer and Andrew E. Aplin
Cancer Immunol Res September 1 2020 (8) (9) 1114-1121; DOI: 10.1158/2326-6066.CIR-19-0743

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Activation of CD8+ T Cells Contributes to Antitumor Effects of CDK4/6 Inhibitors plus MEK Inhibitors
Jessica L.F. Teh, Dan A. Erkes, Phil F. Cheng, Manoela Tiago, Nicole A. Wilski, Conroy O. Field, Inna Chervoneva, Mitch P. Levesque, Xiaowei Xu, Reinhard Dummer and Andrew E. Aplin
Cancer Immunol Res September 1 2020 (8) (9) 1114-1121; DOI: 10.1158/2326-6066.CIR-19-0743
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • CD47–SIRPα Checkpoint Controls CD18 Activation via Kindlin3
  • Triple Therapy Depletes Immune-Potentiating Myeloid Cells
  • Inducing CTLs through DLnano-vaccines to Target Cancer
Show more Priority Brief
  • 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