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
    • Journal Sections
    • Subscriptions
    • Reviewing
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • 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
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • 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 Discovery
Cancer Discovery
  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Reviewing
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • 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
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

News in Brief

LIGHT May Improve Immune Checkpoint Blockade Response

DOI: 10.1158/2159-8290.CD-NB2016-042 Published June 2016
  • Article
  • Info & Metrics
Loading

A protein that recruits tumor-infiltrating lymphocytes has the potential to improve response rates to immune checkpoint blockade, a recent study suggests. The researchers demonstrate that having insufficient T cells inside tumors explains why many patients do not respond to immunotherapy.

Researchers have long suspected that significant T-cell infiltration of patients' tumors is necessary for response to PD-L1 blockade, but the theory is difficult to confirm clinically and had never been proven in animal models. In this study, investigators developed mouse models of PD-L1–expressing tumors, both with and without significant T-cell infiltration. An analysis of the tumor tissue revealed that tumors with significant T-cell infiltration were well controlled by PD-L1 inhibitors, whereas those with few T cells were unresponsive.

“We've shown that sufficient T-cell infiltration, not necessarily PD-L1 expression, determines response to PD-L1 blockade,” says the study's senior investigator Yang-Xin Fu, PhD, professor of pathology and immunology at The University of Texas Southwestern Medical Center in Dallas. The results are published in Cancer Cell.

Fu's team set out to discover whether increasing T-cell infiltration of tumors could overcome resistance to PD-L1 blockade. The researchers had previously shown in the lab that upregulation of the costimulatory molecule LIGHT, a tumor necrosis factor (TNF) superfamily member, in established tumors triggers production of chemokines that recruit high numbers of T cells to the tumor microenvironment, leading to tumor regression.

In this study, they tested the strategy in mice by attaching an EGFR antibody to LIGHT to target EGFR-expressing tumors with low T-cell infiltration. They found that anti-EGFR–guided LIGHT led to tumor regression in the mice whereas anti–PD-L1 therapy alone had no effect. However, neither PD-L1 inhibitors nor LIGHT, individually, were sufficient to control large tumors, possibly because LIGHT also increased the level of PD-L1 expression. As a result, combining PD-L1 blockade with LIGHT may be the most effective treatment strategy, the researchers concluded.

“Our data suggest that combining treatments that inhibit PD-L1 expression while increasing T-cell infiltration of tumors can overcome resistance to checkpoint blockade,” says Fu. “LIGHT appears to allow tumors to regain their ability to respond to checkpoint blockade.”

The combination of PD-L1 inhibitors and anti–CTLA-4 is currently the most promising strategy being tested to increase the response rate to checkpoint blockade, Fu notes. However, anti–CTLA-4 also appears to work best when tumors have preexisting T-cell infiltration, suggesting that it may be more effective in combination with LIGHT than with another checkpoint inhibitor. However, this theory has not yet been tested, adds Fu.

The findings lay the foundation for developing multiple novel classes of antibody-based drugs, notes Timothy A. Chan, MD, PhD, vice chair of radiation oncology and director of the Translational Oncology Division at Memorial Sloan Kettering Cancer Center in New York, NY. EGFR, as well as HER2, are strong candidates for antibodies because they are overexpressed in some human cancers.

“This may lead to strategies to make HER2-positive breast cancer more immunogenic,” says Chan. “Using LIGHT may be one way to convert nonimmunogenic, anti–PD1-refractory tumors into responsive ones.”

However, he adds, because the current study was conducted in mice, “it still remains to be seen whether LIGHT will work in humans.” –Janet Colwell

  • ©2016 American Association for Cancer Research.
View Abstract
PreviousNext
Back to top
Cancer Discovery: 6 (6)
June 2016
Volume 6, Issue 6
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Discovery 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.
LIGHT May Improve Immune Checkpoint Blockade Response
(Your Name) has forwarded a page to you from Cancer Discovery
(Your Name) thought you would be interested in this article in Cancer Discovery.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
LIGHT May Improve Immune Checkpoint Blockade Response
Cancer Discov June 1 2016 (6) (6) OF9; DOI: 10.1158/2159-8290.CD-NB2016-042

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
LIGHT May Improve Immune Checkpoint Blockade Response
Cancer Discov June 1 2016 (6) (6) OF9; DOI: 10.1158/2159-8290.CD-NB2016-042
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
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Congress Approves Increase in Cancer Funding
  • Tasmanian Devil Facial Tumor Disease Turns Endemic
  • Proteomics Sharpens Brain Tumor Genomic Analysis
Show more News in Brief
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • OnlineFirst
  • Current Issue
  • Past Issues

Info For

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Discovery

  • About the Journal
  • Editors
  • Journal Sections
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Discovery
eISSN: 2159-8290
ISSN: 2159-8274

Advertisement