Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • 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

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Molecular and Cellular Biology, Genetics

Abstract 2885: Somatic mutation of STAT3 leads to the preferential Th17 differentiation in human naïve CD4-positive cells and favor TCR-mediated proliferation

Ramona Crescenzo, Valentina Fragliasso, Marcello Gaudiano, Marco Pizzi and Giorgio Inghirami
Ramona Crescenzo
Weill Cornell Medicine, New York, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Valentina Fragliasso
Weill Cornell Medicine, New York, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marcello Gaudiano
Weill Cornell Medicine, New York, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marco Pizzi
Weill Cornell Medicine, New York, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giorgio Inghirami
Weill Cornell Medicine, New York, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM2016-2885 Published July 2016
  • Article
  • Info & Metrics
Loading
Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA

Abstract

Intro: Mature Th17 lymphocytes play a key role in the host defenses against bacteria and fungi although unchecked Th17 activation can lead to autoimmune disorders, inflammation and cancer. The engagement of CD4+ naïve T-cells via IL6 and TGFβ favors a Th17 differentiation program, which requires the presence of IL21 and IL23 to reach a complete maturation and the maintenance of Th17 phenotype. The Th17 differentiation requires multiple lineage defining transcription factors (i.e. RORα, RORγt, and STAT3) and the activation of STAT3 signaling, which regulates a plethora of factors (i.e. RORγt, IL23R), is required for the full execution of the Th17 program. We have recently shown that JAK1/STAT3 activating mutations in Anaplastic Large cell Lymphomas (ALCL) are oncogenic, but it is unknown their protumorigenic contribution in modulating/derailing the host microenviroment and the host responses.

Methods: 50 FFPE ALCLs were investigated with pSTAT3, GATA3, RORγ and T-Bet antibodies using a dual color approach. CD4+ CD62L+ CD25- CD45RAhi CD4+ naïve cells of healthy donor were sorted and cultured (7 days) in KBM (IL23 (25ng/ml), IL6 (25ng/ml), IL21 (25ng/ml), IL1β (12,5ng/ml), TGFβ (5ng/ml) + 1% FBS and anti-CD3/CD28 beads (1:50). Forced expressions of WT or mutated Y640F (YF) STAT3 were achieved via lentiviral transduction. STAT3 qRTPCR, luciferase assay, ATPlite, and ELISA were used as readouts on samples collected at day 7 post-transduction.

Results: IHC stains showed that pSTAT3+ ALCL preferentially co-expressed nuclear RORγ (p<000.1). Conversely, GATA3+ ALK- ALCL samples were preferentially STAT3-/RORγ- (12/14). Forced expression of STAT3 led to a higher expression of IL23R, RORγt and IL17, compared to controls cells. No statistically differences were seen in cell proliferation or metabolic levels in these conditions. Naïve YF STAT3 CD4 cells, when cultured w/o IL2 (100U/ml) + IL6 + anti-CD3/CD28 beads, were able to efficiently proliferate up to 20 days overcome controls and WT STAT3 cells. Lastly, transfection of HEK293T cells with YF STAT3 in the presence of an IL17 promoter reporter cassette, led to a significant higher luciferase expression levels than control or WT STAT3 transfected cells.

Conclusions: Our data demonstrated that the ectopic expression of STAT3 leads to a robust Th17 differentiation of CD4 naïve T-cells and YF STAT3 sustains their growth overtime in the presence of TCR signaling. The preferential expression of RORγ in pSTAT3+ ALCL (ALK+ and mutated STAT3 ALK-ALCL) suggest that the deregulated activation of STAT3 can regulate the plasticity of the neoplastic cells favoring the recruitment of inflammatory host cells within the neoplastic lesions. Additional studies are underway to define the lymphoma-host interactions and the role of JAK TKI in controlling the lymphoma growth and in modulating the pro-tumorigenic inflammatory phenotype of Patient Derived Tumor Xenograft

Citation Format: Ramona Crescenzo, Valentina Fragliasso, Marcello Gaudiano, Marco Pizzi, Giorgio Inghirami. Somatic mutation of STAT3 leads to the preferential Th17 differentiation in human naïve CD4-positive cells and favor TCR-mediated proliferation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2885.

  • ©2016 American Association for Cancer Research.
Previous
Back to top
Cancer Research: 76 (14 Supplement)
July 2016
Volume 76, Issue 14 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

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

Thank you for sharing this Cancer 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.
Abstract 2885: Somatic mutation of STAT3 leads to the preferential Th17 differentiation in human naïve CD4-positive cells and favor TCR-mediated proliferation
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract 2885: Somatic mutation of STAT3 leads to the preferential Th17 differentiation in human naïve CD4-positive cells and favor TCR-mediated proliferation
Ramona Crescenzo, Valentina Fragliasso, Marcello Gaudiano, Marco Pizzi and Giorgio Inghirami
Cancer Res July 15 2016 (76) (14 Supplement) 2885; DOI: 10.1158/1538-7445.AM2016-2885

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract 2885: Somatic mutation of STAT3 leads to the preferential Th17 differentiation in human naïve CD4-positive cells and favor TCR-mediated proliferation
Ramona Crescenzo, Valentina Fragliasso, Marcello Gaudiano, Marco Pizzi and Giorgio Inghirami
Cancer Res July 15 2016 (76) (14 Supplement) 2885; DOI: 10.1158/1538-7445.AM2016-2885
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
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Molecular and Cellular Biology, Genetics

  • Abstract LB-336: Specific serine phosphorylation of IRE-1 controls enhanced splicing of XBP-1 and regulated IRE-1-dependent decay (RIDD)
  • Abstract LB-276: Characterizing tumorigenesis of ovarian cancer across metastatic tumors and circulating, cell-free DNA
  • Abstract LB-335: Induction of Ribosomal Checkpoint Induced Senescence (RCIS) for the treatment of liver cancer
Show more 3

Poster Presentations - Proffered Abstracts

  • Abstract LB-236: Risk of tMDS/AML after chemotherapy for first primary lymphoid malignancy, 2000-2013
  • Abstract LB-001: Impact of direct physician engagement with racial/ethnic minorities for oncology clinical trial access and accrual model
  • Abstract LB-107: EV-TRACK: transparent reporting and centralizing knowledge of extracellular vesicles to support the validation of extracellular vesicle biomarkers in cancer research
Show more 3

Poster Presentations - Transcriptional Regulation and Gene Expression in Human Malignancies

  • Abstract 2891: High throughput single cell gene expression profiling by multiplex qPCR
  • Abstract 2889: Loss of 4E-BP1 function promotes EMT and metastasis via translational activation of snail
  • Abstract 2868: Mechanisms of transcriptional regulation of FOXO3 by cofactors upon PI3K/AKT/mTOR inhibition
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement