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
  • 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
  • Search More

    Advanced Search

Research Watch

Low-Heterogeneity Melanomas Are More Immunogenic and Less Aggressive

DOI: 10.1158/2159-8290.CD-RW2019-144 Published November 2019
  • Article
  • Info & Metrics
  • PDF
Loading
  • Major Finding: In mouse models of melanoma, lower intratumoral heterogeneity (ITH) correlated with lower tumor growth.

  • Concept: In patient data, high levels of ITH predicted reduced survival and poorer response to immunotherapy.

  • Impact: This study shows that ITH is an important factor in melanoma and may be a prognostic biomarker.

Recent studies have indicated that intratumoral heterogeneity (ITH) may be an important factor in determining the immune response to tumors, but the cause is not known, and the potential interplay between ITH and tumor mutational burden (TMB) is unclear. In a cohort of patients with melanoma, Wolf, Bartok, and colleagues found that those with low levels of ITH had improved survival rates compared with those with higher levels of ITH. When injected into immunocompetent mice, melanoma cells exposed to UVB irradiation (which increases both ITH and TMB) formed tumors that grew at an increased rate compared with non-irradiated melanoma cells. To distinguish between the effects of ITH and TMB, single-cell clones (SCC) from the UVB-irradiated melanoma cells were generated. Injected SCCs formed tumors that grew at reduced rates compared with tumors grown from the heterogeneous parental cells, indicating that low levels of ITH are associated with decreased tumor aggressiveness independently of any effects of TMB. In severely immunocompromised mice, tumors grown from SCCs exhibited as much growth as those grown from the high-ITH, UVB-irradiated parental cells, implying that it was immune rejection that caused the reduced growth of SCC-derived tumors in the immunocompetent mice used in the prior experiments. Correspondingly, SCC-derived tumors were more immunogenic than tumors derived from the high-ITH parental cells. Experiments in which tumors were derived from defined mixtures of different SCC populations revealed that tumor aggressiveness could be largely explained by both the number of clones injected and their genetic diversity. Highlighting the potential clinical relevance of these findings, a meta-analysis of data from patients with melanoma from four prior studies showed that the number of clones and their genetic diversity mediated response to immunotherapy, with tumors having higher diversity being associated with worse outcomes. Collectively, these data establish ITH as an independent factor that may be associated with prognosis and response to immunotherapy and suggest that this phenomenon can be explained by increased immunogenicity of low-ITH tumors.

Wolf Y, Bartok O, Patkar S, Eli GB, Cohen S, Litchfield K, et al. UVB-induced tumor heterogeneity diminishes immune response in melanoma. Cell 2019;179:219–35.e21.

Notes

Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.

  • ©2019 American Association for Cancer Research.
View Abstract
PreviousNext
Back to top
Cancer Discovery: 9 (11)
November 2019
Volume 9, Issue 11
  • 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 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.
Low-Heterogeneity Melanomas Are More Immunogenic and Less Aggressive
(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
Low-Heterogeneity Melanomas Are More Immunogenic and Less Aggressive
Cancer Discov November 1 2019 (9) (11) 1483; DOI: 10.1158/2159-8290.CD-RW2019-144

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Low-Heterogeneity Melanomas Are More Immunogenic and Less Aggressive
Cancer Discov November 1 2019 (9) (11) 1483; DOI: 10.1158/2159-8290.CD-RW2019-144
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
    • Notes
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

Research Watch

  • Epstein–Barr Virus–Induced Antitumor Immune Response May Be Harnessable
  • FBXO44 Silences Repetitive Elements during DNA Replication in Cancer
  • Cryo-EM Structures Reveal Mechanism of Anticancer MCT1 Inhibitors
Show more Research Watch

Melanoma

  • Midkine Promotes Immunosuppression and Reduces Immunotherapy Efficacy
  • SMAD7 Loss Promotes Phenotype Switching–Independent Melanoma
Show more Melanoma
  • 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