Human KIT+ myeloid cells facilitate visceral metastasis by melanoma

J Exp Med. 2021 Jun 7;218(6):e20182163. doi: 10.1084/jem.20182163.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • CD11b Antigen / metabolism
  • Cell Line, Tumor
  • Cohort Studies
  • Humans
  • Leukocyte Common Antigens / metabolism
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Mice
  • Mice, Inbred NOD
  • Myeloid Cells / metabolism*
  • Myeloid Cells / pathology*
  • Prognosis
  • Proto-Oncogene Proteins c-kit / metabolism*

Substances

  • Biomarkers
  • CD11b Antigen
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit
  • Leukocyte Common Antigens