Evidence map›Paper›PMID 25720800›Full record

ArticleCancer research2015

IL10 and PD-1 Cooperate to Limit the Activity of Tumor-Specific CD8+ T Cells.

Zhaojun Sun, Julien Fourcade, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, John M Kirkwood, Hassane M Zarour

Registry-linked trialAbstract read
In one paragraph

Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04663126 (Pilot Study to Test the Feasibility of IV Injected Tc-99m-tilmanocept for Imaging of M2-like Tumour Associated Macrophages in Metastatic Melanoma), which is not on this map. Cited by 120 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% 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.

NCT04663126 early_phase1terminatednot on this mapstarted 2021, after this paper: background citation

Pilot Study to Test the Feasibility of IV Injected Tc-99m-tilmanocept for Imaging of M2-like Tumour Associated Macrophages in Metastatic Melanoma

TypeinterventionalSponsorJohn O. PriorRan2021 to 2023Enrolled5ConditionsMelanomaArmsTc-99m tilmanocept
3 · Its place in the literature

Who cites it

120 citing papers in PubMed, 1 synthesis or guideline pooled it, 190 citations in OpenAlex.

  1. Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Pooled it
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  7. Exercise and CD8Journal of molecular medicine (Berlin, Germany) · 2026
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  14. Utility of [Cancer immunology, immunotherapy : CII · 2025
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60 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

7 authors at 1 institution in 1 country.

Zhaojun SunDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Julien FourcadeDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Ornella PaglianoDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Joe-Marc ChauvinDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Cindy SanderDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
John M KirkwoodDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Hassane M ZarourDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. zarourhm@upmc.edu.
University of Pittsburgh · US

Funding

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
Melanoma Vaccines with Peptides, Protein and AdjuvantR01CA112198 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZAROUR, HASSANE M · 2005 to 2009
$1.6M
Reversing melanoma-induced T cell dysfunctionR01CA157467 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZAROUR, HASSANE M · 2011 to 2015
$1.5M
NCI NIH HHS P50 CA121973NCI NIH HHS P50CA121973NCI NIH HHS R01 CA112198NCI NIH HHS R01CA112198NCI NIH HHS R01 CA157467NCI NIH HHS R01CA157467
6 · The paper itself

Abstract

Immune checkpoint inhibitors show great promise as therapy for advanced melanoma, heightening the need to determine the most effective use of these agents. Here, we report that programmed death-1(high) (PD-1(high)) tumor antigen (TA)-specific CD8(+) T cells present at periphery and at tumor sites in patients with advanced melanoma upregulate IL10 receptor (IL10R) expression. Multiple subsets of peripheral blood mononucleocytes from melanoma patients produce IL10, which acts directly on IL10R(+) TA-specific CD8(+) T cells to limit their proliferation and survival. PD-1 blockade augments expression of IL10R by TA-specific CD8(+) T cells, thereby increasing their sensitivity to the immunosuppressive effects of endogenous IL10. Conversely, IL10 blockade strengthened the effects of PD-1 blockade in expanding TA-specific CD8(+) T cells and reinforcing their function. Collectively, our findings offer a rationale to block both IL10 and PD-1 to strengthen the counteraction of T-cell immunosuppression and to enhance the activity of TA-specific CD8(+) T cell in advanced melanoma patients.

Indexed as

Tumor EscapeAntibodiesCD8-Positive T-LymphocytesCells, CulturedHumansImmune ToleranceInterleukin-10Lymphocyte ActivationLymphocytes, Tumor-InfiltratingMelanomaProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellReceptors, Interleukin-10Skin NeoplasmsAntibodiesIL10 protein, humanInterleukin-10PDCD1 protein, humanProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellReceptors, Interleukin-10

Identifiers

PMID25720800
PMCPMC4401638
OpenAlexW2146591037

What OpenQuestion holds

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Registered trials

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.