Wang Chengpan, Shi Jieyi, Xu Jietian, Fu Qiaoyu, Ding Youpeng, Yang Jessie, Liu Binbin, Gao Qiang, Qin Jie, Liang Chunmin
Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China.
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
Front Oncol. 2022 Jan 25;12:815326. doi: 10.3389/fonc.2022.815326. eCollection 2022.
NLRC3 (NLR family caspase recruitment domain containing 3) has been reported as a factor of inhibiting inflammatory responses. It's role in HCC (hepatocellular carcinoma) is still unknown. In this study we firstly used the GEO (Gene Expression Omnibus) database and mIHC (multiple immunohistochemical analysis) with TMAs (tumor tissue microarrays) of HCC patients to evaluate NLRC3 levels. The tumor-bearing mouse models were also established with NLRC3 over-expressing and knock-down Hepal-6 cells to assess its effect. The data showed high NLRC3 expression was related with favorable overall survival (=0.0386) and disease-free survival (=0.0458). In addition, NLRC3 expression showed a positive correlation between CD8 T cells infiltration. , NLRC3-overexpressing Hepal-6 tumors showed increased CD8 T cell infiltration. NLRC3-knockdown Hepa1-6 tumors displayed decreased CD8 T cell infiltration. At the same time, we also found the positive correlations between NLRC3 and CCL5 (C-C motif chemokine ligand 5, <0.0001, R = 0.2372) as well as CXCL9 (C-X-C motif chemokine ligand 9, <0.0001, R = 0.2338) expressions. So NLRC3 high expression represents a novel predictor for positive survival outcomes in HCC patients, and NLRC3 is involved in CD8 T cell infiltration, which is correlated with increased CCL5 and CXCL9 in TME (tumor microenvironment). This study implies that boosting NLRC3 is a promising treatment to enhance survival in HCC patients.
NLRC3(含半胱天冬酶招募结构域的NLR家族3)已被报道为抑制炎症反应的一个因子。其在肝癌(肝细胞癌)中的作用仍不清楚。在本研究中,我们首先使用基因表达综合数据库(GEO)以及对肝癌患者肿瘤组织芯片(TMAs)进行多重免疫组织化学分析(mIHC)来评估NLRC3水平。还构建了过表达和敲低NLRC3的Hepal-6细胞的荷瘤小鼠模型来评估其作用。数据显示,NLRC3高表达与良好的总生存期(=0.0386)和无病生存期(=0.0458)相关。此外,NLRC3表达与CD8 T细胞浸润呈正相关。过表达NLRC3的Hepal-6肿瘤中CD8 T细胞浸润增加。敲低NLRC3的Hepa1-6肿瘤中CD8 T细胞浸润减少。同时,我们还发现NLRC3与CCL5(C-C基序趋化因子配体5,<0.0001,R = 0.2372)以及CXCL9(C-X-C基序趋化因子配体