The Journal of experimental medicine
J Exp Med 2021 Jun 7; 218(6):e20182163
CA195712; P30 JAX Cancer Center grant
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.
Yu, Chun I.; Martinek, Jan; Wu, Te-Chia; Kim, Kyung In; George, Joshy; Ahmadzadeh, Elaheh; Maser, Richard S.; Marches, Florentina; Metang, Patrick; Authie, Pierre; Oliveira, Vanessa K P; Wang, Victor G; Chuang, Jeffrey; Robson, Paul; Banchereau, Jacques; and Palucka, Karolina, "Human KIT+ myeloid cells facilitate visceral metastasis by melanoma." (2021). Faculty Research 2021. 85.