The Immunosuppressive Niche of Soft-Tissue Sarcomas is Sustained by Tumor-Associated Macrophages and Characterized by Intratumoral Tertiary Lymphoid Structures.
Adolescent
Adult
Aged
Aged, 80 and over
B-Lymphocytes
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Child
Child, Preschool
Drug Resistance, Neoplasm
/ immunology
Female
Humans
Immune Checkpoint Inhibitors
/ pharmacology
Lymphocytes, Tumor-Infiltrating
/ immunology
Male
Middle Aged
Neoplasms, Complex and Mixed
/ drug therapy
Rhabdomyosarcoma
/ drug therapy
Tertiary Lymphoid Structures
/ immunology
Tumor Escape
Tumor Microenvironment
/ drug effects
Tumor-Associated Macrophages
/ immunology
Young Adult
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
received:
23
10
2019
revised:
01
03
2020
accepted:
20
04
2020
pubmed:
26
4
2020
medline:
3
11
2021
entrez:
26
4
2020
Statut:
ppublish
Résumé
Clinical trials with immune checkpoint inhibition in sarcomas have demonstrated minimal response. Here, we interrogated the tumor microenvironment (TME) of two contrasting soft-tissue sarcomas (STS), rhabdomyosarcomas and undifferentiated pleomorphic sarcomas (UPS), with differing genetic underpinnings and responses to immune checkpoint inhibition to understand the mechanisms that lead to response. Utilizing fresh and formalin-fixed, paraffin-embedded tissue from patients diagnosed with UPS and rhabdomyosarcomas, we dissected the TME by using IHC, flow cytometry, and comparative transcriptomic studies. Our results demonstrated both STS subtypes to be dominated by tumor-associated macrophages and infiltrated with immune cells that localized near the tumor vasculature. Both subtypes had similar T-cell densities, however, their Our work in STS revealed an immunosuppressive TME dominated by myeloid cells, which may be overcome with activation of T cells that traffic into the tumor. In rhabdomyosarcomas, targeting T cells found within TLS may be key to achieve antitumor response.
Identifiants
pubmed: 32332015
pii: 1078-0432.CCR-19-3416
doi: 10.1158/1078-0432.CCR-19-3416
pmc: PMC8772618
mid: NIHMS1748036
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4018-4030Subventions
Organisme : NCI NIH HHS
ID : T32 CA060441
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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