Journal of Inflammation Research (Jan 2023)
C-Type Lectin Receptors-Triggered Antifungal Immunity May Synergize with and Optimize the Effects of Immunotherapy in Hepatocellular Carcinoma
Abstract
Jinkun Xia,1,2,* Haoran Ding,1,* Shujun Liu,3 Ran An,1,2 Xiaolei Shi,1– 3 Ming Chen,1 Haozhen Ren1– 3 1Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Institute of Hepatobiliary Surgery, Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haozhen Ren; Ming Chen, Email [email protected]; [email protected]: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system worldwide, and there is a lack of effective treatment for late-stage HCC. Recent experimental studies have demonstrated that dysfunction of the intestinal flora has a significant impact on hepatocarcinogenesis. The pathophysiological link between the intestine, its microbiota, and the liver has been described as the “gut-liver axis”. Dysbiosis of the intestinal flora and increased permeability of the intestinal wall are closely associated with liver pathology through the immune response. The “gut-liver axis” theory has been applied to the clinical study of the pathogenesis and treatment of HCC. The intestinal fungal community, as part of the gut microbiome, has a significant impact on human health and disease, while relatively little research has been done in HCC. In this study, we performed a comprehensive analysis of the expression and potential biological functions of the fungal recognition receptors C-type lectin receptors (CLRs) (Dectin-1, Dectin-2, Dectin-3, and Mincle) in HCC. We found that CLRs were downregulated in HCC, and their expressions were correlated with the clinical prognosis of HCC patients. Further studies suggested that the expression of CLRs were significantly correlated with immune infiltration and immunotherapy efficacy in HCC. Based on previous studies and our findings, we hypothesize that intestinal fungal communities and CLRs-triggered antifungal immunity have a key role in the pathogenesis of HCC, and these findings may provide new perspectives and targets for HCC immunotherapy.Keywords: hepatocellular carcinoma, mycobiome, fungus, immunity, C-type lectin receptor, gut-liver axis
