RT Journal Article
SR Electronic
T1 Cholangiocarcinoma presents a distinct myeloid-derived suppressor cell signature compared to other hepatobiliary cancers
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 554600
DO 10.1101/554600
A1 Defne Bayik
A1 Adam J. Lauko
A1 Gustavo A. Roversi
A1 Emily Serbinowski
A1 Lou-Anne Acevedo-Moreno
A1 Christopher Lanigan
A1 Mushfig Orujov
A1 Alice Lo
A1 Tyler J. Alban
A1 Daniel J. Silver
A1 J. Mark Brown
A1 Daniela S. Allende
A1 Federico N. Aucejo
A1 Justin D. Lathia
YR 2019
UL http://biorxiv.org/content/early/2019/12/11/554600.abstract
AB Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that are increased in patients with numerous malignancies including viral-derived hepatocellular carcinoma (HCC). Here, we report an elevation of MDSC in other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). Investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors further established that the frequency of antigen-presenting cells was limited compared to benign lesions suggesting that primary and metastatic hepatobiliary cancers have distinct peripheral and tumoral myeloid signatures. Bioinformatics analysis of the Cancer Genome Atlas demonstrated that a high MDSC score in HCC patients predicted poor disease outcome. Mechanistic studies indicated that the oncometabolite D-2-hydroxyglutarate resulting from isocitrate dehydrogenase 1 mutation could be a limiting factor of MDSC accumulation in CCA patients. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, they may comprise suitable targets for effective immunotherapy approaches.AFPAlpha-fetoproteinαKGαAlpha-ketoglutarateASTAspartate aminotransferaseALTAlanine transaminaseAPCAntigen-presenting cellsCCACholangiocarcinomaCEACarcinoembryonic antigenCRLMColorectal liver metastasesD2HGD-2-HydroxyglutarateDCDendritic cellgMDSCGranulocytic myeloid-derived suppressor cellsHCCHepatocellular carcinomaMDSCMyeloid-derived suppressor cellsmMDSCMonocytic myeloid-derived suppressor cellsNETNeuroendocrine tumorPBMCPeripheral blood mononuclear cellsTCGAThe Cancer Genome AtlasTregT regulatory cellsWBCWhite blood cells