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 Articles

Multidimensional Analyses of Donor Memory-Like NK Cells Reveal New Associations with Response after Adoptive Immunotherapy for Leukemia

Melissa M. Berrien-Elliott, Amanda F. Cashen, Celia C. Cubitt, Carly C. Neal, Pamela Wong, Julia A. Wagner, Mark Foster, Timothy Schappe, Sweta Desai, Ethan McClain, Michelle Becker-Hapak, Jennifer A. Foltz, Matthew L. Cooper, Natalia Jaeger, Sridhar Nonavinkere Srivatsan, Feng Gao, Rizwan Romee, Camille N. Abboud, Geoffrey L. Uy, Peter Westervelt, Meagan A. Jacoby, Iskra Pusic, Keith E. Stockerl-Goldstein, Mark A. Schroeder, John DiPersio and Todd A. Fehniger
Melissa M. Berrien-Elliott
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Melissa M. Berrien-Elliott
  • For correspondence: tfehnige@wustl.edu melissa.berrien@wustl.edu
Amanda F. Cashen
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Celia C. Cubitt
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Celia C. Cubitt
Carly C. Neal
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pamela Wong
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pamela Wong
Julia A. Wagner
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark Foster
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy Schappe
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sweta Desai
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ethan McClain
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michelle Becker-Hapak
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer A. Foltz
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jennifer A. Foltz
Matthew L. Cooper
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Natalia Jaeger
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sridhar Nonavinkere Srivatsan
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Feng Gao
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rizwan Romee
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Camille N. Abboud
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Geoffrey L. Uy
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Geoffrey L. Uy
Peter Westervelt
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Meagan A. Jacoby
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Iskra Pusic
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keith E. Stockerl-Goldstein
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Keith E. Stockerl-Goldstein
Mark A. Schroeder
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mark A. Schroeder
John DiPersio
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Todd A. Fehniger
1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: tfehnige@wustl.edu melissa.berrien@wustl.edu
DOI: 10.1158/2159-8290.CD-20-0312 Published December 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

Natural killer (NK) cells are an emerging cancer cellular therapy and potent mediators of antitumor immunity. Cytokine-induced memory-like (ML) NK cellular therapy is safe and induces remissions in patients with acute myeloid leukemia (AML). However, the dynamic changes in phenotype that occur after NK-cell transfer that affect patient outcomes remain unclear. Here, we report comprehensive multidimensional correlates from ML NK cell–treated patients with AML using mass cytometry. These data identify a unique in vivo differentiated ML NK–cell phenotype distinct from conventional NK cells. Moreover, the inhibitory receptor NKG2A is a dominant, transcriptionally induced checkpoint important for ML, but not conventional NK-cell responses to cancer. The frequency of CD8α+ donor NK cells is negatively associated with AML patient outcomes after ML NK therapy. Thus, elucidating the multidimensional dynamics of donor ML NK cells in vivo revealed critical factors important for clinical response, and new avenues to enhance NK-cell therapeutics.

Significance: Mass cytometry reveals an in vivo memory-like NK-cell phenotype, where NKG2A is a dominant checkpoint, and CD8α is associated with treatment failure after ML NK–cell therapy. These findings identify multiple avenues for optimizing ML NK–cell immunotherapy for cancer and define mechanisms important for ML NK–cell function.

This article is highlighted in the In This Issue feature, p. 1775

Footnotes

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

  • Cancer Discov 2020;10:1854–71

  • Received March 13, 2020.
  • Revision received July 17, 2020.
  • Accepted August 18, 2020.
  • Published first August 21, 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 Discovery: 10 (12)
December 2020
Volume 10, Issue 12
  • 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.
Multidimensional Analyses of Donor Memory-Like NK Cells Reveal New Associations with Response after Adoptive Immunotherapy for Leukemia
(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
Multidimensional Analyses of Donor Memory-Like NK Cells Reveal New Associations with Response after Adoptive Immunotherapy for Leukemia
Melissa M. Berrien-Elliott, Amanda F. Cashen, Celia C. Cubitt, Carly C. Neal, Pamela Wong, Julia A. Wagner, Mark Foster, Timothy Schappe, Sweta Desai, Ethan McClain, Michelle Becker-Hapak, Jennifer A. Foltz, Matthew L. Cooper, Natalia Jaeger, Sridhar Nonavinkere Srivatsan, Feng Gao, Rizwan Romee, Camille N. Abboud, Geoffrey L. Uy, Peter Westervelt, Meagan A. Jacoby, Iskra Pusic, Keith E. Stockerl-Goldstein, Mark A. Schroeder, John DiPersio and Todd A. Fehniger
Cancer Discov December 1 2020 (10) (12) 1854-1871; DOI: 10.1158/2159-8290.CD-20-0312

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Multidimensional Analyses of Donor Memory-Like NK Cells Reveal New Associations with Response after Adoptive Immunotherapy for Leukemia
Melissa M. Berrien-Elliott, Amanda F. Cashen, Celia C. Cubitt, Carly C. Neal, Pamela Wong, Julia A. Wagner, Mark Foster, Timothy Schappe, Sweta Desai, Ethan McClain, Michelle Becker-Hapak, Jennifer A. Foltz, Matthew L. Cooper, Natalia Jaeger, Sridhar Nonavinkere Srivatsan, Feng Gao, Rizwan Romee, Camille N. Abboud, Geoffrey L. Uy, Peter Westervelt, Meagan A. Jacoby, Iskra Pusic, Keith E. Stockerl-Goldstein, Mark A. Schroeder, John DiPersio and Todd A. Fehniger
Cancer Discov December 1 2020 (10) (12) 1854-1871; DOI: 10.1158/2159-8290.CD-20-0312
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
    • Results
    • Discussion
    • Methods
    • 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

  • Correction of FPR1 Defect
  • Somatic Mutations and Cancer Risk in Skin across the Body
  • ATR Inhibitor BAY 1895344 in Advanced Solid Tumors
Show more Research Articles
  • 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