Human KIT(+) myeloid cells facilitate visceral metastasis by melanoma

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.