Evidence map›Paper›PMID 36074145›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022

Ewing Sarcoma and Osteosarcoma Have Distinct Immune Signatures and Intercellular Communication Networks.

Anthony R Cillo, Elina Mukherjee, Nathanael G Bailey, Sayali Onkar, Jessica Daley, Claudia Salgado, Xiang Li, Dongyan Liu, Sarangarajan Ranganathan, Melissa Burgess and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
8.6field-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.

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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Spatial Transcriptomics Analysis of Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027
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  18. Spatial Profiling Identifies Tumor-Associated Stroma Enrichment and MIF as Potential Immunotherapy Targets in Primary Ewing Sarcomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
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5 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

16 authors at 2 institutions in 3 countries.

Anthony R CilloDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-3213-3129
Elina MukherjeeDepartment of Pediatrics, Division of Pediatric Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0001-9750-7219
Nathanael G BaileyDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-6747-680X
Sayali OnkarDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-5890-290X
Jessica DaleyDepartment of Pediatrics, Division of Pediatric Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0001-5133-448X
Claudia SalgadoDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-8821-1296
Xiang LiDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-3961-9156
Dongyan LiuDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0003-4357-4867
Sarangarajan RanganathanDivision of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.ORCID 0000-0001-6214-9167
Melissa BurgessDepartment of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-5753-1422
John SembratDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.ORCID 0000-0003-4108-803X
Kurt WeissDepartment of Orthopedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0003-3859-728X
Rebecca WattersDepartment of Orthopedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0001-7486-7510
Tullia C Bruno *Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-6433-0207
Dario A A Vignali *Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0002-2771-5992
Kelly M Bailey *Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0003-3925-3243
University of Pittsburgh · USCincinnati Children's Hospital Medical Center · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
Synergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dario AA Vignali · 2015 to 2026
$30.8M
Training in Cellular & Molecular Mechanisms of Tumor RejectionT32CA082084 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Robert J Binder, Dario AA Vignali · 1999 to 2026
$9.2M
Molecular Basis of Pediatric DiseaseK12HD052892 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TERENCE S. DERMODY · 2007 to 2026
$6.5M
Regulatory T cells and the tumor microenvironmentR35CA263850 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dario AA Vignali · 2021 to 2026
$5.4M
Research Training Program for Pediatric Subspecialty FellowsT32HD071834 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TERENCE S. DERMODY · 2013 to 2026
$4.7M
DNA Damage and Immunogenicity in Ewing SarcomaK08CA252178 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAILEY, KELLY · 2021 to 2025
$765k
NCI NIH HHS K08 CA252178NCI NIH HHS P30 CA047904NCI NIH HHS R35 CA263850NCI NIH HHS T32 CA082084NIAID NIH HHS P01 AI108545NICHD NIH HHS K12 HD052892NICHD NIH HHS T32 HD071834
6 · The paper itself

Abstract

purposeEwing sarcoma and osteosarcoma are primary bone sarcomas occurring most commonly in adolescents. Metastatic and relapsed disease are associated with dismal prognosis. Although effective for some soft tissue sarcomas, current immunotherapeutic approaches for the treatment of bone sarcomas have been largely ineffective, necessitating a deeper understanding of bone sarcoma immunobiology. EXPERIMENTAL

designMultiplex immunofluorescence analysis of immune infiltration in relapsed versus primary disease was conducted. To better understand immune states and drivers of immune infiltration, especially during disease progression, we performed single-cell RNA sequencing (scRNAseq) of immune populations from paired blood and bone sarcoma tumor samples.

resultsOur multiplex immunofluorescence analysis revealed increased immune infiltration in relapsed versus primary disease in both Ewing sarcoma and osteosarcoma. scRNAseq analyses revealed terminally exhausted CD8+ T cells expressing co-inhibitory receptors in osteosarcoma and an effector T-cell subpopulation in Ewing sarcoma. In addition, distinct subsets of CD14+CD16+ macrophages were present in Ewing sarcoma and osteosarcoma. To determine pathways driving tumor immune infiltration, we conducted intercellular communication analyses and uncovered shared mechanisms of immune infiltration driven by CD14+CD16+ macrophages and unique pathways of immune infiltration driven by CXCL10 and CXCL12 in osteosarcoma.

conclusionsOur study provides preclinical rationale for future investigation of specific immunotherapeutic targets upon relapse and provides an invaluable resource of immunologic data from bone sarcomas.

Indexed as

Bone NeoplasmsOsteosarcomaSarcomaSarcoma, EwingAdolescentCell CommunicationHumansNeoplasm Recurrence, Local

Identifiers

PMID36074145
PMCPMC9669190
OpenAlexW4294958512

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.