RESUMEN
We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of â¼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease.
Asunto(s)
Carcinoma Hepatocelular/patología , Células Endoteliales/metabolismo , Microambiente Tumoral/genética , Adulto , Animales , Carcinoma Hepatocelular/genética , Línea Celular , Modelos Animales de Enfermedad , Células Endoteliales/patología , Femenino , Receptor 2 de Folato/metabolismo , Perfilación de la Expresión Génica/métodos , Humanos , Hígado/patología , Neoplasias Hepáticas/genética , Macrófagos/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Receptores Notch/genética , Receptores Notch/metabolismo , Transducción de Señal/genética , Transcriptoma/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Icteric Hepatocellular Carcinoma (HCC) is known to cause intraluminal biliary obstruction by one of three mechanisms: hemobilia from the tumour, migration of tumor debris, or continuous growth along the biliary tree. It is however a very rare presentation of HCC and an important differential diagnosis in the approach to obstructive jaundice. We report a case of a recurrent intraductal hepatocellular carcinoma. The patient initially underwent surgical resection of segment five HCC nine months ago with clear margins. The patient now presents with obstructive jaundice and imaging showed a right intraductal tumour involving the confluence, left and common hepatic ducts. He underwent a right hepatectomy and bile duct tumour thrombectomy despite the apparent absence of a parenchymal tumour. Histological examination showed a 2 mm focus of parenchymal tumour with extension of the tumour into the bile duct. In this case report, we reviewed the literature and describe the different surgical approaches to intraductal hepatocellular carcinomas and discuss the pathological aspects of these bile duct tumour thrombus. We report the favourable outcome of surgical resection for intraductal hepatocellular carcinoma and emphasize that intraductal HCC is not a late stage of disease and adequate surgical resection can still provide a reasonable disease free survival.