Evidence map›Paper›PMID 40198126›Full record

ArticleJCI insight2025

Increased fatty acid delivery by tumor endothelium promotes metastatic outgrowth.

Deanna N Edwards, Shan Wang, Kelby Kane, Wenqiang Song, Laura C Kim, Verra M Ngwa, Yoonha Hwang, Kevin Ess, Mark R Boothby, Jin Chen

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Deanna N EdwardsDepartment of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Shan WangDepartment of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Kelby KaneProgram in Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA.
Wenqiang SongDepartment of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Laura C KimProgram in Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA.
Verra M NgwaDepartment of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Yoonha HwangDepartment of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Kevin EssDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Denver, Colorado, USA.
Mark R BoothbyDepartment of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jin ChenDepartment of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARY Kay WASHINGTON · 2002 to 2026
$29.9M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI OWEN P MCGUINNESS · 2012 to 2026
$29.3M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
MULTIDISCIPLINARY BASIC RESEARCH TRAINING IN CANCERT32CA009592 · NCI · VANDERBILT UNIVERSITY · PI Justin M Balko, Julie A Rhoades (Sterling) · 1987 to 2026
$10.4M
Ephrin-A1 in Tumor-Endothelial Interaction During MetastasisR01CA095004 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CHEN, JIN · 2003 to 2019
$4.6M
Effect of tumor cell glutamine metabolism on anti-tumor immunity in TNBCR01CA250506 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BOOTHBY, MARK R, CHEN, JIN · 2020 to 2024
$2.4M
Identifying mTOR Dependent Periods During Brain DevelopmentR01NS118580 · NINDS · VANDERBILT UNIVERSITY · PI ESS, KEVIN C, IHRIE, REBECCA A · 2020 to 2024
$2.1M
Vascular regulation of fatty acid transport in metastatic tumor outgrowthR01CA271176 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jin Chen · 2023 to 2026
$2.0M
The Role of Vascular Endothelial Glutaminase in Tumor Vessel Normalization and Response to TherapyF31CA243148 · NCI · VANDERBILT UNIVERSITY · PI NGWA, VERRA · 2019 to 2021
$93k
Targeting mLST8 in mTORC2-dependent lung cancerF31CA220804 · NCI · VANDERBILT UNIVERSITY · PI KIM, LAURA C · 2017 to 2019
$88k
BLRD VA I01 BX000134BLRD VA IK6 BX005391NCI NIH HHS F31 CA220804NCI NIH HHS F31 CA243148NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA095004NCI NIH HHS R01 CA250506NCI NIH HHS R01 CA271176NCI NIH HHS T32 CA009592NEI NIH HHS P30 EY008126NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS U24 DK059637NINDS NIH HHS R01 NS118580
6 · The paper itself

Abstract

Metastatic outgrowth in distant microscopic niches requires sufficient nutrients, including fatty acids (FAs), to support tumor growth and to generate an immunosuppressive tumor microenvironment (TME). However, despite the important role of FAs in metastasis, the regulation of FA supply in metastatic niches has not been defined. In this report, we show that tumor endothelium actively promotes outgrowth and restricts antitumor cytolysis by transferring FAs into developing metastatic tumors. We describe a process of transendothelial FA delivery via endosomes that requires mTORC1 activity. Thus, endothelial cell-specific targeted deletion of Raptor (RptorECKO), a unique component of the mTORC1 complex, significantly reduced metastatic tumor burden that was associated with improved markers of T cell cytotoxicity. Low-dose everolimus that selectively inhibited endothelial mTORC1 improves immune checkpoint responses in metastatic disease models. This work reveals the importance of transendothelial nutrient delivery to the TME, highlighting a future target for therapeutic development.

Indexed as

Fatty AcidsAnimalsCell Line, TumorEndothelial CellsEverolimusFemaleHumansMechanistic Target of Rapamycin Complex 1MiceNeoplasm MetastasisRegulatory-Associated Protein of mTORTumor MicroenvironmentEverolimusFatty AcidsMechanistic Target of Rapamycin Complex 1Regulatory-Associated Protein of mTORCancer immunotherapyEndothelial cellsImmunologyMetabolismOncology

Identifiers

PMID40198126
PMCPMC12128997

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.