Abstract 1750: Human KIT+myeloid cells facilitate visceral organ colonization by melanoma

Abstract Metastasis is a major risk factor for poor melanoma outcome, but mechanisms supporting distant organ colonization by melanoma are not fully understood. Here, we found that metastatic melanoma tumors from patients are infiltrated by CD33+ myeloid cells. To determine the role of CD33+ cells in melanoma metastasis, we used NSG mice humanized by engraftment of human CD34+ hematopoietic progenitor cells and transgenic expression of human hematopoietic cytokines SCF/GM-CSF/IL-3 (SGM3). Humanized (h)NSG-SGM3 mice enabled development of human CD33+ myeloid cells in the bone marrow and peripheral tissues, and when implanted subcutaneously with human melanoma cell line, supported melanoma colonization of the spleen, liver, lung, and kidneys. Melanoma growth in distant organs was dependent on host SGM3 expression and facilitated by human CD33+ myeloid cells. Deeper characterization attributed this activity to a rare human IL-3- and SCF-dependent CD33+CD11b+CD117+ progenitor cell subset comprising <4% of the total CD45+ leukocyte population. Metastatic tumor-infiltrating CD33+ cells from patients and hNSG-SGM3 mice showed converging transcriptional profiles. Single-cell RNAseq analysis identified a gene signature of a KIT/CD117 expressing CD33+ subset that correlated with decreased overall survival in TCGA melanoma samples. Thus, human CD33+CD11b+CD117+ myeloid cells facilitate metastatic colonization of distant organs by melanoma, representing a novel candidate biomarker as well as a therapeutic opportunity for metastatic melanoma. Citation Format: Chun I. Yu, Jan Martinek, Te-Chia Wu, Kyung In Kim, Joshy George, Elaheh Ahmadzadeh, Rick Maser, Florentina Marches, Patrick Metang, Pierre Authie, Vanessa K. Oliveira, Victor G. Wang, Jeffrey H. Chuang, Paul Robson, Jacques Banchereau, Karolina Palucka. Human KIT+myeloid cells facilitate visceral organ colonization by melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1750.