Tumor-induced generation of splenic erythroblast-like Ter-cells promotes tumor progression

Journal article

Identifying tumor-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding cancer as a systemic disease. Nevertheless, how primary tumor-induced non-leukocyte populations in distal organs contribute to systemic spread remains poorly defined. Here, we report one population of tumor-inducible, erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119+CD45−CD71+ phenotype. Ter-cells are enriched in the enlarged spleen of hosts bearing advanced tumors and facilitate tumor progression by secreting neurotrophic factor artemin into the blood. Transforming growth factor β (TGF-β) and Smad3 activation are important in Ter-cell generation. In vivo blockade of Ter-cell-derived artemin inhibits hepatocellular carcinoma (HCC) growth, and artemin deficiency abolishes Ter-cells’ tumor-promoting ability. We confirm the presence of splenic artemin-positive Ter-cells in human HCC patients and show that significantly elevated serum artemin correlates with poor prognosis. We propose that Ter-cells and the secreted artemin play important roles in cancer progression with prognostic and therapeutic implications.

Authors: Han, Y; Liu, Q; Hou, J; Gu, Y; Zhang, Y

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell
• Volume: 173
• Issue: 3
• Pages: 634-648.e12
• Publication date: 2018-03-28
• Acceptance date: 2018-02-26
• DOI: 10.1016/j.cell.2018.02.061
• EISSN: 1097-4172
• ISSN: 0092-8674
• Pmid: 29606356
• Language: English
• Keywords: erythroblast-like; artemin; hepatocellular carcinoma; prognosis biomarker; Ter-cell; Ter-119; cancer immunotherapy