Evidence map›Paper›PMID 36479153›Full record

ArticleOncoimmunology2022

Fibroblasts and macrophages cooperate to create a pro-tumorigenic and immune resistant environment via activation of TGF-β/IL-6 pathway in neuroblastoma.

Kevin Louault, Tania Porras, Meng-Hua Lee, Sakunthala Muthugounder, Rebekah J Kennedy, Laurence Blavier, Emily Sarte, G Esteban Fernandez, Fusheng Yang, Bruce R Pawel and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncoimmunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
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

40 citing papers in PubMed, 49 citations in OpenAlex.

  1. Integration of Bulk RNA Sequencing and Single-Cell Sequencing to Identify Prognostic Genes Associated With MCDRGs in Neuroblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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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

13 authors at 4 institutions in 1 country.

Kevin LouaultCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
Tania PorrasCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
Meng-Hua LeeCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
Sakunthala MuthugounderCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
Rebekah J KennedyCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
Laurence BlavierCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
Emily SarteCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
G Esteban FernandezThe Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Fusheng YangDepartment of Pathology, University of Southern California, Los Angeles, CA, USA.
Bruce R PawelDepartment of Pathology, University of Southern California, Los Angeles, CA, USA.
Hiroyuki ShimadaDepartments of Pathology and Pediatrics, Stanford University, Stanford, CA, USA.
Shahab AsgharzadehCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
Yves A DeClerckCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, USA.
University of Southern California · USChildren's Hospital of Los Angeles · USSouthern California University for Professional Studies · USStanford University · US

Funding

Tumor microenvironment-dependent therapy resistanceP01CA217959 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Kimberly Stegmaier · 2017 to 2026
$20.7M
NCI NIH HHS P01 CA217959
6 · The paper itself

Abstract

Tumor-associated macrophages (TAM) and cancer-associated fibroblasts (CAF) and their precursor mesenchymal stromal cells (MSC) are often detected together in tumors, but how they cooperate is not well understood. Here, we show that TAM and CAF are the most abundant nonmalignant cells and are present together in untreated human neuroblastoma (NB) tumors that are also poorly infiltrated with T and natural killer (NK) cells. We then show that MSC and CAF-MSC harvested from NB tumors protected human monocytes (MN) from spontaneous apoptosis in an interleukin (IL)-6 dependent mechanism. The interactions of MN and MSC with NB cells resulted in a significant induction or increase in the expression of several pro-tumorigenic cytokines/chemokines (TGF-β1, MCP-1, IL-6, IL-8, and IL-4) but not of anti-tumorigenic cytokines (TNF-α, IL-12) by MN or MSC, while also inducing cytokine expression in quiescent NB cells. We then identified a TGF-β1/IL-6 pathway where TGF-β1 stimulated the expression of IL-6 in NB cells and MSC, promoting TAM survival. Evidence for the contribution of TAM and MSC to the activation of this pathway was then provided in xenotransplanted NB tumors and patients with primary tumors by demonstrating a direct correlation between the presence of CAF and p-SMAD2 and p-STAT3. The data highlight a new mechanism of interaction between TAM and CAF supporting their pro-tumorigenic function in cancer.

Indexed as

FibroblastsInterleukin-6MacrophagesNeuroblastomaTransforming Growth Factor beta1AnimalsHumansInterleukin-6Transforming Growth Factor beta1cancer-associated fibroblastscytokines/chemokinesimmune resistanceinflammationinterleukin-6mesenchymal stromal cellsneuroblastomatransforming growth factor-β1tumor-associated macrophagestumor microenvironment

Identifiers

PMID36479153
PMCPMC9721439
OpenAlexW4310519822

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.