Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization.

Thumbnail
View / Download
5.1 Mb
Date
2018-01
Authors
Zhao, Fei
Xiao, Christine
Evans, Kathy S
Theivanthiran, Tbalamayooran
DeVito, Nicholas
Holtzhausen, Alisha
Liu, Juan
Liu, Xiaojing
Boczkowski, David
Nair, Smita
Locasale, Jason W
Hanks, Brent A
Show More
(12 total)
Repository Usage Stats
162
views
57
downloads
Abstract
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter. This FAO shift increased the protoporphyrin IX prosthetic group of indoleamine 2,3-dioxgenase-1 (IDO) while suppressing interleukin(IL)-6 and IL-12 cytokine expression, culminating in enhanced IDO activity and the generation of regulatory T cells. We demonstrated that blockade of this pathway augmented anti-melanoma immunity, enhanced the activity of anti-PD-1 antibody immunotherapy, and suppressed disease progression in a transgenic melanoma model. This work implicates a role for tumor-mediated metabolic reprogramming of local DCs in immune evasion and immunotherapy resistance.
Type
Journal article
Subject
Dendritic Cells
Cell Line
Animals
Mice, Transgenic
Mice
Melanoma
Fatty Acids
PPAR gamma
Immunoblotting
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Polymerase Chain Reaction
Paracrine Communication
Signal Transduction
Female
Male
beta Catenin
Wnt-5a Protein
Permalink
https://hdl.handle.net/10161/17695
Published Version (Please cite this version)
10.1016/j.immuni.2017.12.004
Publication Info
Zhao, Fei; Xiao, Christine; Evans, Kathy S; Theivanthiran, Tbalamayooran; DeVito, Nicholas; Holtzhausen, Alisha; ... Hanks, Brent A (2018). Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization. Immunity, 48(1). pp. 147-160.e7. 10.1016/j.immuni.2017.12.004. Retrieved from https://hdl.handle.net/10161/17695.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
  • Scholarly Articles
More Info
Show full item record

Scholars@Duke

DeVito

Nicholas Christian DeVito

Medical Instructor in the Department of Medicine
I am an instructor of Medical Oncology who primarily treats patients with gastrointestinal malignancies. My laboratory and translational research is focused on tumor immune evasion and immunotherapy, with a specific interest in dendritic cell tolerance.
Hanks

Brent A. Hanks

Associate Professor of Medicine
We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers
Locasale

Jason Locasale

Associate Professor of Pharmacology and Cancer Biology
Our research interests are in three interconnected areas:  1) Quantitative and computational biology of metabolism. 2) The role of diet and pharmacological therapeutics in shaping metabolic pathways in health and cancer.  3) The interaction of metabolism and epigenetics.  Each of these synergistic areas utilizes the metabolomics technologies we develop along with our expertise in computational and molecular biology.
Nair

Smita K Nair

Professor in Surgery
I have 22 years of experience in the field of cancer vaccines and immunotherapy and I am an accomplished T cell immunologist. Laboratory website:https://surgery.duke.edu/immunology-inflammation-immunotherapy-laboratory Current projects in the Nair Laboratory:1] Dendritic cell vaccines using tumor-antigen encoding RNA (mRNA, total tumor RNA, amplified tumor mRNA)<br
Alphabetical list of authors with Scholars@Duke profiles.
Open Access

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy

Rights for Collection: Scholarly Articles


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University