Evidence map›Paper›PMID 35879777›Full record

ArticleJournal of translational medicine2022

Co-expression of TNF receptors 1 and 2 on melanomas facilitates soluble TNF-induced resistance to MAPK pathway inhibitors.

Cindy A Sander, Elizabeth A Rush, Jian Shi, Lidia M R B Arantes, Raymond J Tesi, Mark A Ross, Michael J Calderon, Simon C Watkins, John M Kirkwood, Robert L Ferris and 2 more

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

Article in Journal of translational medicine, 2022. 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
0.3field-weighted citation impact, top 45% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Knockouts ofInternational journal of molecular sciences · 2023
    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

12 authors at 1 institution in 2 countries.

Cindy A SanderUPMC Hillman Cancer Center, University of Pittsburgh, L2.19 Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA.
Elizabeth A RushUPMC Hillman Cancer Center, University of Pittsburgh, L2.19 Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA.
Jian ShiUPMC Hillman Cancer Center, University of Pittsburgh, L2.19 Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA.
Lidia M R B ArantesUPMC Hillman Cancer Center, University of Pittsburgh, L2.19 Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA.
Raymond J TesiINmune Bio, La Jolla, CA, USA.
Mark A RossDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Michael J CalderonDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Simon C WatkinsDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
John M KirkwoodUPMC Hillman Cancer Center, University of Pittsburgh, L2.19 Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA.
Robert L FerrisUPMC Hillman Cancer Center, University of Pittsburgh, L2.19 Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA.
Lisa H ButterfieldUPMC Hillman Cancer Center, University of Pittsburgh, L2.19 Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA.
Lazar VujanovicUPMC Hillman Cancer Center, University of Pittsburgh, L2.19 Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA. vujanovicl@upmc.edu.ORCID 0000-0003-1729-8619
University of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
Therapuetic Immune Targeting of EphA2 Expressed by Melanoma & Its Tumor-AssociateP50CA121973 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIRKWOOD, JOHN MUNN · 2008 to 2018
$22.9M
NCI NIH HHS P30 CA047904NIH HHS P50 CA121973
6 · The paper itself

Abstract

backgroundThe effectiveness of MAPK pathway inhibitors (MAPKi) used to treat patients with BRAF-mutant melanoma is limited by a range of resistance mechanisms, including soluble TNF (solTNF)-mediated NF-kB signaling. solTNF preferentially signals through type-1 TNF receptor (TNFR1), however, it can also bind to TNFR2, a receptor that is primarily expressed on leukocytes. Here, we investigate the TNFR2 expression pattern on human BRAF

methodsFlow cytometry was used to test TNFR1, TNFR2 and CD271 expression on, as well as NF-kB phosphorylation in human BRAF-mutant melanoma. The ability of melanoma cell lines to acquire MAPKi resistance in response to recombinant or macrophage-derived TNF was evaluated using the MTT cytotoxicity assay. Gene editing was implemented to knock out or knock in TNF receptors in melanoma cell lines. Knockout and knock-in cell line variants were employed to assess the intrinsic roles of these receptors in TNF-induced resistance to MAPKi. Multicolor immunofluorescence microscopy was utilized to test TNFR2 expression by melanoma in patients receiving MAPKi therapy.

resultsTNFR1 and TNFR2 are co-expressed at various levels on 4/7 BRAF

conclusionsOur data suggest that TNFR2 is essential to solTNF-induced MAPKi resistance and a possible biomarker to identify melanoma patients that can benefit from solTNF-targeting therapies.

Indexed as

MelanomaReceptors, Tumor Necrosis Factor, Type IIHumansNF-kappa BProtein Kinase InhibitorsProto-Oncogene Proteins B-rafReceptors, Tumor Necrosis Factor, Type INF-kappa BProtein Kinase InhibitorsProto-Oncogene Proteins B-rafReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIBRAFCD271Drug resistanceInhibitorsMEKMelanomaSoluble TNFTNF receptor 1TNF receptor 2

Identifiers

PMID35879777
PMCPMC9310383
OpenAlexW4287147799

What OpenQuestion 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 OpenQuestion graph.