Hepatobiliary malignancies have distinct peripheral myeloid-derived suppressor cell signatures and tumor myeloid cell profiles

肝胆恶性肿瘤具有独特的外周髓系抑制细胞特征和肿瘤髓系细胞特征

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作者:Defne Bayik, Adam J Lauko, Gustavo A Roversi, Emily Serbinowski, Lou-Anne Acevedo-Moreno, Christopher Lanigan, Mushfig Orujov, Alice Lo, Tyler J Alban, Adam Kim, Daniel J Silver, Laura E Nagy, J Mark Brown, Daniela S Allende, Federico N Aucejo, Justin D Lathia

Abstract

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 MDSCs in the peripheral blood of patients with other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), and colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). The 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 dataset demonstrated that a high MDSC score in HCC patients is associated with poor disease outcome. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, these cells may represent suitable targets for effective immunotherapy approaches.

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