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[HetColi] – Lect2 controls inflammatory monocytes to constrain the growth and progression of hepatocellular carcinoma. - Published on 21 08 2018
2018 Aug 2. doi: 10.1002/hep.30140. 

L'Hermitte A1,2,3, Pham S1,2,3, Cadoux M1,2,3, Couchy G3,4,5,6, Caruso S3,4,5,6, Anson M1,2,3, Crain-Denoyelle AM1,2,3, Celton-Morizur S1,2,3, Yamagoe S7, Zucman-Rossi J3,4,5,6, Desdouets C1,2,3, Couty JP1,2,3,4.

Abstract

Leukocyte cell-derived chemotaxin-2 (LECT2) was originally identified as a hepatocyte secreted chemokine-like factor and a positive target of β-catenin signaling. Here, we dissected out the mechanisms by which LECT2 modulates hepatocellular carcinoma (HCC) development using both HCC mouse models and human HCC samples. We have demonstrated that LECT2 exhibits dual ability as it has profound repercussions on the tumor phenotype itself and the immune microenvironment. Its absence confers Ctnnb-1-mutated tumor hepatocytes a stronger ability to undergo epithelial to mesenchymal transition (EMT) and fosters the accumulation of pejorative inflammatory monocytes harboring immunosuppressive properties and strong tumor promoting potential. Consistent with our HCC mouse model, low level of LECT2 in human HCC is strongly associated with high tumor grade and the presence of inflammatory infiltrates emphasizing the clinical value of LECT2 in human liver tumorigenesis.

CONCLUSION:

our findings have demonstrated that LECT2 is an key player of liver tumorigenesis as its absence reshapes the TME and the tumor phenotype revealing LECT2 as a promising immunotherapeutic option for HCC. This article is protected by copyright. All rights reserved.

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This French program is organized by ITMO Cancer, in collaboration with ITMO BCDE (Cell Biology, Development and Evolution) and ITMO Technologies for Health of the National Alliance for Life Sciences and Health (AVIESAN) with the National Cancer Institute (INCA) and Inserm within the framework of the Cancer Plan. Operational management is entrusted to Inserm.
It was launch in order to develop a critical mass of resources and skills in order to conduct interdisciplinary research projects in the field of functional heterogeneity of cellular tumor relations in their ecosystem: the "HTE Program".

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