A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade.
Animals
Biomarkers, Tumor
/ immunology
Breast Neoplasms
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Female
Gene Expression Regulation, Neoplastic
/ immunology
Humans
Immunotherapy
Mammary Neoplasms, Experimental
/ immunology
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Transcriptome
/ immunology
Tumor Microenvironment
/ immunology
bilateral tumor model
breast cancer
immune checkpoint blockade
predictive biomarkers
tumor immune 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:
22 09 2020
22 09 2020
Historique:
pubmed:
11
9
2020
medline:
18
11
2020
entrez:
10
9
2020
Statut:
ppublish
Résumé
Immune checkpoint blockade (ICB) is efficacious in many diverse cancer types, but not all patients respond. It is important to understand the mechanisms driving resistance to these treatments and to identify predictive biomarkers of response to provide best treatment options for all patients. Here we introduce a resection and response-assessment approach for studying the tumor microenvironment before or shortly after treatment initiation to identify predictive biomarkers differentiating responders from nonresponders. Our approach builds on a bilateral tumor implantation technique in a murine metastatic breast cancer model (E0771) coupled with anti-PD-1 therapy. Using our model, we show that tumors from mice responding to ICB therapy had significantly higher CD8
Identifiants
pubmed: 32907939
pii: 2002806117
doi: 10.1073/pnas.2002806117
pmc: PMC7519254
doi:
Substances chimiques
Biomarkers, Tumor
0
Programmed Cell Death 1 Receptor
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
23684-23694Subventions
Organisme : NCI NIH HHS
ID : R01 CA229851
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197743
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI039671
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA080124
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA208205
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI056299
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA224348
Pays : United States
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: R.K.J. received an honorarium from Amgen; consultant fees from Merck, Pfizer, SPARC, and SynDevRx; owns equity in Enlight and SynDevRx; and serves on the scientific advisory board of Accurius Therapeutics and 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. A.H.S. has patents on the PD-1 pathway licensed by Roche/Genentech and Novartis, consults for Novartis, is on the scientific advisory boards for Surface Oncology, Sqz Biotech, Elstar Therapeutics, Elpiscience, Selecta, and Monopteros, and has research funding from Merck, Novartis, Roche, and Quark Ventures. R.K.J. and D.A.T. are co-authors on a 2020 Cold Spring Harbor Laboratory meeting report.
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