Blocking CXCR4 alleviates desmoplasia, increases T-lymphocyte infiltration, and improves immunotherapy in metastatic breast cancer.
carcinoma-associated fibroblasts
immune checkpoint blockade
metastatic breast cancer
tumor desmoplasia
tumor microenvironment
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
05 03 2019
05 03 2019
Historique:
pubmed:
1
2
2019
medline:
9
4
2020
entrez:
1
2
2019
Statut:
ppublish
Résumé
Metastatic breast cancers (mBCs) are largely resistant to immune checkpoint blockade, but the mechanisms remain unclear. Primary breast cancers are characterized by a dense fibrotic stroma, which is considered immunosuppressive in multiple malignancies, but the stromal composition of breast cancer metastases and its role in immunosuppression are largely unknown. Here we show that liver and lung metastases of human breast cancers tend to be highly fibrotic, and unlike primary breast tumors, they exclude cytotoxic T lymphocytes (CTLs). Unbiased analysis of the The Cancer Genome Atlas database of human breast tumors revealed a set of genes that are associated with stromal T-lymphocyte exclusion. Among these, we focused on
Identifiants
pubmed: 30700545
pii: 1815515116
doi: 10.1073/pnas.1815515116
pmc: PMC6410779
doi:
Substances chimiques
CXCR4 protein, human
0
Receptors, CXCR4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4558-4566Subventions
Organisme : NCI NIH HHS
ID : T32 CA073479
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA224348
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007627
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA098706
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197743
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA080124
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA208205
Pays : United States
Commentaires et corrections
Type : CommentIn
Déclaration de conflit d'intérêts
Conflict of interest statement: R.K.J. received an honorarium from Amgen; consultant fees from Merck, Ophthotech, Pfizer, SPARC, SynDevRx, and XTuit; owns equity in Enlight, Ophthotech, and SynDevRx; and serves on the Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund, and Tekla World Healthcare Fund. Neither any reagent nor any funding from these organizations was used in this study. R.K.J. and D.T.F. are co-authors of a 2018 National Cancer Institute-Tumor Immune Microenvironment Workshop meeting report.
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