Evidence map›Paper›PMID 24848257›Full record

ArticleScience translational medicine2014

Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy.

Steven L Highfill, Yongzhi Cui, Amber J Giles, Jillian P Smith, Hua Zhang, Elizabeth Morse, Rosandra N Kaplan, Crystal L Mackall

2 registry-linked trialsOpen access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 520 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
520citing papers in PubMed, 1 pooled it
17.7field-weighted citation impact, top 1% 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.

NCT02914405 phase1active not recruitingnot on this mapstarted 2018, after this paper: background citation

A Phase I Study of 131-1 mIBG Followed by Nivolumab and Dinutuximab Beta in Children With Relapsed/Refractory Neuroblastoma

TypeinterventionalSponsorUniversity Hospital Southampton NHS Foundation TrustRan2018 to 2026Enrolled44ConditionsNeuroblastomaArmsNivolumab, Ch14.18/CHO
NCT03447678 phase2unknown statusnot on this mapstarted 2018, after this paper: background citation

Phase II Study to Test Pembrolizumab (MK-3475) in First Line Treatment of Advanced NSCLC Patients With PD-L1 Low Tumors (<50%)_ PEOPLE TRIAL (Pembrolizumab in Pd-L1 Low Expressors).

TypeinterventionalSponsorFondazione IRCCS Istituto Nazionale dei Tumori, MilanoRan2018 to 2022Enrolled65ConditionsNon Small Cell Lung Cancer (NSCLC)ArmsPembrolizumab
3 · Its place in the literature

Who cites it

520 citing papers in PubMed, 1 synthesis or guideline pooled it, 744 citations in OpenAlex.

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  16. Targeting mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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460 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Steven L HighfillPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yongzhi CuiPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Amber J GilesPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jillian P SmithPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hua ZhangPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Elizabeth MorsePediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Rosandra N KaplanPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Crystal L MackallPediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. cm35c@nih.gov.
National Cancer Institute · USNational Institutes of Health · US

Funding

Tumor Microenvironment in Cancer ProgressionZIABC011332 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KAPLAN, ROSANDRA NATASHA · 2010 to 2025
$10.8M
Biomarkers and Therapeutic Targets in Tumor Microenvironment and MetastasisZIABC011334 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KAPLAN, ROSANDRA NATASHA · 2010 to 2025
$10.8M
Immunobiology of Pediatric TumorsZIABC011073 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MACKALL, CRYSTAL · 2009 to 2015
$8.4M
Tumor and Metastasis BiologyZ01BC010566 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KHANNA, CHAND · 2005 to 2008
$1.8M
Immunobiology and Immunotherapy of Pediatric TumorsZ01SC010289 · SC · CLINICAL SCIENCES · PI MACKALL, CRYSTAL L. · 1999 to 2007
$985k
Developing Immune Based TherapiesZ01BC011072 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MACKALL, CRYSTAL · 2008 to 2008
$686k
Intramural NIH HHS Z01 BC010566Intramural NIH HHS Z01 BC011072Intramural NIH HHS Z01 SC010289
6 · The paper itself

Abstract

Suppression of the host's immune system plays a major role in cancer progression. Tumor signaling of programmed death 1 (PD1) on T cells and expansion of myeloid-derived suppressor cells (MDSCs) are major mechanisms of tumor immune escape. We sought to target these pathways in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood. Murine RMS showed high surface expression of PD-L1, and anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 had limited benefit. RMS induced robust expansion of CXCR2(+)CD11b(+)Ly6G(hi) MDSCs, and CXCR2 deficiency prevented CD11b(+)Ly6G(hi) MDSC trafficking to the tumor. When tumor trafficking of MDSCs was inhibited by CXCR2 deficiency, or after anti-CXCR2 monoclonal antibody therapy, delayed anti-PD1 treatment induced significant antitumor effects. Thus, CXCR2(+)CD11b(+)Ly6G(hi) MDSCs mediate local immunosuppression, which limits the efficacy of checkpoint blockade in murine RMS. Human pediatric sarcomas also produce CXCR2 ligands, including CXCL8. Patients with metastatic pediatric sarcomas display elevated serum CXCR2 ligands, and elevated CXCL8 is associated with diminished survival in this population. We conclude that accumulation of MDSCs in the tumor bed limits the efficacy of checkpoint blockade in cancer. We also identify CXCR2 as a novel target for modulating tumor immune escape and present evidence that CXCR2(+)CD11b(+)Ly6G(hi) MDSCs are an important suppressive myeloid subset in pediatric sarcomas. These findings present a translatable strategy to improve the efficacy of checkpoint blockade by preventing trafficking of MDSCs to the tumor site.

Indexed as

AdolescentAdultAnimalsAntibodies, MonoclonalAntigens, LyAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCase-Control StudiesCD11b AntigenCell Line, TumorChemokine CXCL1ChemotaxisChildChild, PreschoolCytokinesFemaleAntibodies, MonoclonalAntigens, LyB7-H1 AntigenCD11b AntigenCd274 protein, mouseChemokine CXCL1CXCL1 protein, humanCXCL8 protein, humanCytokinesInterleukin-8Ly6G antigen, mouseReceptors, Interleukin-8B

Identifiers

PMID24848257
PMCPMC6980372
OpenAlexW2171524684

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.