4.7 Article

Human KIT+ myeloid cells facilitate visceral metastasis by melanoma

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JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 6, 页码 -

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ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20182163

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  1. Jackson Laboratory
  2. National Institutes of Health [CA195712]
  3. Department of Defense [W81XWH1710010]
  4. Merck
  5. U.S. Department of Defense (DOD) [W81XWH1710010] Funding Source: U.S. Department of Defense (DOD)

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Metastasis of melanoma significantly worsens prognosis; the CD33+CD11b+CD117+ myeloid cells could serve as a potential biomarker and therapeutic target for metastatic 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.

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