RT Journal Article
SR Electronic
T1 Malignant liver cancers have distinct myeloid-derived suppressor cell signatures
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 554600
DO 10.1101/554600
A1 Defne Bayik
A1 Emily Serbinowski
A1 Adam Lauko
A1 Gustavo A. Roversi
A1 Lou-Anne Acevedo-Moreno
A1 Christopher Lanigan
A1 Mushfig Orujov
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/2019/02/19/554600.abstract
AB Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immunosuppressive cells that limit immune response in patients with cancer. It has been reported that circulating MDSC frequencies are increased in patients with viral-derived hepatocellular carcinoma (HCC). In this study, we compared the MDSC frequency of 100 patients with primary hepatobiliary malignancies or metastatic liver lesions. Non-viral HCC patients and patients with neuroendocrine tumors (NET) had the highest level of MDSCs (CD33+CD11b+HLA-DRlow/-), followed by colorectal carcinoma patients with liver metastases (CRLM). In contrast, MDSC levels were not significantly elevated in cholangiocarcinoma (CCA) cases. Another immunosuppressive cell population, regulatory T cells were not augmented in peripheral blood of patients with hepatobiliary malignancies or liver metastasis. Investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors showed that the frequency of CD33+ and HLA-DR+ cells marking antigen-presenting cells were limited compared to benign lesions. Bioinformatic analysis of the Cancer Genome Atlas demonstrated that a high MDSC score in HCC patients predicted poor disease outcome.Conclusion These data suggest that primary and metastatic hepatobiliary cancers have distinct immune activation status and MDSC signatures. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, they may comprise suitable targets for effective immunotherapy approaches.AbbreviationsAFPAlpha-fetoproteinASTAspartate aminotransferaseALTAlanine transaminaseAPCAntigen-presenting cellsCCACholangiocarcinomaCEACarcinoembryonic antigenCRLMColorectal liver metastasesDCDendritic cellgMDSCGranulocytic myeloid-derived suppressor cellsHCCHepatocellular carcinomaMDSCMyeloid-derived suppressor cellsmMDSCMonocytic myeloid-derived suppressor cellsNETNeuroendocrine tumorPBMCPeripheral blood mononuclear cellsTCGAThe Cancer Genome AtlasTregT regulatory cellsWBCWhite blood cells