Evidence map›Paper›PMID 20068175›Full record

ArticleCancer research2010

Modulation of T-cell activation by malignant melanoma initiating cells.

Tobias Schatton, Ute Schütte, Natasha Y Frank, Qian Zhan, André Hoerning, Susanne C Robles, Jun Zhou, F Stephen Hodi, Giulio C Spagnoli, George F Murphy and 1 more

Open access · greenAbstract read
In one paragraph

Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

181 citing papers in PubMed, 284 citations in OpenAlex.

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  10. Programmed cell death protein 1 in cancer cells.Cell communication and signaling : CCS · 2025
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121 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 1 country.

Tobias SchattonTransplantation Research Center, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Ute Schütte
Natasha Y Frank
Qian Zhan
André Hoerning
Susanne C Robles
Jun Zhou
F Stephen Hodi
Giulio C Spagnoli
George F Murphy
Markus H Frank
Dana-Farber Cancer Institute · USVA Boston Healthcare System · USBrigham and Women's Hospital · US

Funding

Targeting Raf in Melanoma: Mechanisms for Effect & Resistance & Opportunities forP50CA093683 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KUPPER, THOMAS S. · 2001 to 2012
$25.8M
Melanoma Stem Cells, Vasculogenesis and Neoplastic ProgressionR01CA138231 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI FRANK, MARKUS H. · 2008 to 2012
$1.7M
ABCB5 P-Glycoprotein in Cancer Multidrug ResistanceR01CA113796 · NCI · BOSTON CHILDREN'S HOSPITAL · PI FRANK, MARKUS H. · 2006 to 2010
$1.5M
Myoregenerative Potential of ABCB5+ ProgenitorsK08NS051349 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI FRANK, NATASHA Y · 2006 to 2010
$670k
NCI NIH HHS 1R01CA113796-01A1NCI NIH HHS 1R01CA138231-01NCI NIH HHS 2P50CA093683-06A20006NCI NIH HHS P50 CA093683NCI NIH HHS R01 CA113796NCI NIH HHS R01 CA138231NINDS NIH HHS K08 NS051349
6 · The paper itself

Abstract

Highly immunogenic cancers such as malignant melanoma are capable of inexorable tumor growth despite the presence of antitumor immunity. Thus, only a restricted minority of tumorigenic malignant cells may possess the phenotypic and functional characteristics needed to modulate tumor-directed immune activation. Here we provide evidence supporting this hypothesis. Tumorigenic ABCB5(+) malignant melanoma initiating cells (MMICs) possessed the capacity to preferentially inhibit IL-2-dependent T-cell activation and to support, in a B7.2-dependent manner, induction of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs). Compared with melanoma bulk cell populations, ABCB5(+) MMICs displayed lower levels of MHC class I, aberrant positivity for MHC class II, and lower expression levels of the melanoma-associated antigens MART-1, ML-IAP, NY-ESO-1, and MAGE-A. Additionally, these tumorigenic ABCB5(+) subpopulations preferentially expressed the costimulatory molecules B7.2 and PD-1, both in established melanoma xenografts and in clinical tumor specimens. In immune activation assays, MMICs inhibited mitogen-dependent human peripheral blood mononuclear cell (PBMC) proliferation and IL-2 production more efficiently than ABCB5(-) melanoma cell populations. Moreover, coculture with ABCB5(+) MMICs increased the abundance of Tregs, in a B7.2 signaling-dependent manner, along with IL-10 production by mitogen-activated PBMCs. Consistent with these findings, MMICs also preferentially inhibited IL-2 production and induced IL-10 secretion by cocultured patient-derived, syngeneic PBMCs. Our findings identify novel T-cell modulatory functions of ABCB5(+) melanoma subpopulations and suggest specific roles for these MMICs in the evasion of antitumor immunity and in cancer immunotherapeutic resistance.

Indexed as

AnimalsAntigens, NeoplasmATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1HumansLeukocytes, MononuclearLymphocyte ActivationMelanomaMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsT-Lymphocytes, RegulatoryABCB5 protein, humanAntigens, NeoplasmATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1

Identifiers

PMID20068175
PMCPMC2883769
OpenAlexW2102265655

What OpenQuestion holds

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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.