Human KIT+ myeloid cells facilitate visceral metastasis by melanoma
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 15, 2021
- Source ID
- 10.1084/jem.20182163
Entities
People
- Chun I Yu
- Elaheh Ahmadzadeh
- Florentina Marches
- Jacques Banchereau
- Jan Martínek
- Jeffrey H Chuang
- Joshy George
- Karolina Palucka
- Kyung In Kim
- Patrick Metang
- Paul Robson
- Pierre Authié
- Rick Maser
- Te-Chia Wu
- Vanessa K.P. Oliveira
- Victor G. Wang
Organizations
- Jackson Laboratory
- National Institutes of Health
- United States Department of Defense
- University of Connecticut