Document Type

Article

Publication Date

6-7-2021

Publication Title

The Journal of experimental medicine

Keywords

JGM, JMG

JAX Source

J Exp Med 2021 Jun 7; 218(6):e20182163

Volume

218

Issue

6

ISSN

1540-9538

PMID

33857287

DOI

https://doi.org/10.1084/jem.20182163

Grant

CA195712; P30 JAX Cancer Center grant

Abstract

Metastasis of melanoma significantly worsens prognosis; thus, therapeutic interventions that prevent metastasis could improve patient outcomes. Here, we show using humanized mice that colonization of distant visceral organs with melanoma is dependent upon a human CD33+CD11b+CD117+ progenitor cell subset comprising <4% of the human CD45+ leukocytes. Metastatic tumor-infiltrating CD33+ cells from patients and humanized (h)NSG-SGM3 mice showed converging transcriptional profiles. Single-cell RNA-seq analysis identified a gene signature of a KIT/CD117-expressing CD33+ subset that correlated with decreased overall survival in a TCGA melanoma cohort. Thus, human CD33+CD11b+CD117+ myeloid cells represent a novel candidate biomarker as well as a therapeutic target for metastatic melanoma.

Comments

We thank patients and healthy donors; T. Helenius, K. Oxley, S. Guha; Flow Cytometry, Microscopy, Single Cell Biology, and Genome Technologies Cores at The Jackson Laboratory for Genomic Medicine; Patient-Derived Xenograft, Research Animal Facility, and Comparative Medicine and Quality Services at The Jackson Laboratory for Mammalian Genetics; and Comparative Medicine at the University of Connecticut Health Center.

This article is available under a Creative Commons License.

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