Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia.
Adolescent
Adult
Animals
Antineoplastic Agents
/ pharmacology
Bone Marrow Transplantation
Case-Control Studies
Child
Child, Preschool
Female
Humans
Infant
Male
Mice, Inbred C57BL
Monocytes
/ immunology
Neoplasm Recurrence, Local
/ immunology
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
/ immunology
Prognosis
Proteome
/ analysis
RNA-Seq
Retrospective Studies
Single-Cell Analysis
Survival Rate
Tumor Microenvironment
/ immunology
Young Adult
acute lymphoblastic leukemia
chemotherapy
immune microenvironment
monocytes
relapse
single cell
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
08 06 2020
08 06 2020
Historique:
received:
24
01
2020
revised:
05
03
2020
accepted:
22
04
2020
pubmed:
30
5
2020
medline:
4
11
2020
entrez:
30
5
2020
Statut:
ppublish
Résumé
A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. We uncover a role for non-classical monocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosis is predictive of pediatric and adult B-ALL patient survival. We show that human B-ALL blasts alter a vascularized microenvironment promoting monocytic differentiation, while depleting leukemia-associated monocytes in B-ALL animal models prolongs disease remission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulators of B-ALL survival supporting new immune-based therapeutic approaches for high-risk B-ALL treatment.
Identifiants
pubmed: 32470390
pii: S1535-6108(20)30214-2
doi: 10.1016/j.ccell.2020.04.015
pmc: PMC7341535
mid: NIHMS1595230
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Proteome
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
867-882.e12Subventions
Organisme : NCI NIH HHS
ID : P01 CA229086
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA202027
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228135
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216421
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA202025
Pays : United States
Organisme : NIH HHS
ID : S10 OD021747
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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