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Lect2 Controls Inflammatory Monocytes to Constrain the Growth and Progression of Hepatocellular Carcinoma
Author(s) -
L’Hermitte Antoine,
Pham Sandrine,
Cadoux Mathilde,
Couchy Gabrielle,
Caruso Stefano,
Anson Marie,
CrainDenoyelle AnneMarie,
CeltonMorizur Séverine,
Yamagoe Satoshi,
ZucmanRossi Jessica,
Desdouets Chantal,
Couty JeanPierre
Publication year - 2019
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.30140
Subject(s) - hepatocellular carcinoma , medicine , inflammation , cancer research , carcinoma , oncology
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 abilities 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 and fosters the accumulation of pejorative inflammatory monocytes harboring immunosuppressive properties and strong tumor‐promoting potential. Consistent with our HCC mouse model, a 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 a key player in liver tumorigenesis because its absence reshapes the tumor microenvironment and the tumor phenotype, revealing LECT2 as a promising immunotherapeutic option for HCC.