Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis.

Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis. Cell Mol Immunol. 2020 Sep 02;: Authors: Zeng X, Zhou J, Xiong Z, Sun H, Yang W, Mok MTS, Wang J, Li J, Liu M, Tang W, Feng Y, Wang HK, Tsang SW, Chow KL, Yeung PC, Wong J, Lai PB, Chan AW, To KF, Chan SL, Xia Q, Xue J, Chen X, Yu J, Peng S, Sung JJ, Kuang M, Cheng AS Abstract The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types. Although a role for cancer cell invasion programs has been well characterized, whether and how liver-intrinsic factors drive metastatic spread is incompletely understood. Here, we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase (CCRK) signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment. Using an inducible liver-specific transgenic model, we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer (CRC) metastasis to the liver, which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) and lacking natural killer T (NKT) cells. Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7% (metastatic tumor weights) in the melanoma and CRC models, respectively. Mechanistically, CCRK activated...
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Tags: Cell Mol Immunol Source Type: research