The role of cd5l in hepatocyte and macrophage response in liver cancer

• Autores: Gemma Aran Canals
• Directores de la Tesis: Maria Rosa Sarrias Fornés (dir. tes.), Lucia Sanjurgo Bouza (codir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2017
• Idioma: español
• Tribunal Calificador de la Tesis: Pau Sancho Bru (presid.), Catalina Casas Louzao (secret.), Joan Sayós Ortega (voc.)
• Programa de doctorado: Programa de Doctorado en Inmunología Avanzada por la Universidad Autónoma de Barcelona
• Materias:
  • Ciencias de la vida
    • Biología celular
    • Inmunología
  • Ciencias médicas
    • Patología
      • Oncología
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• Resumen

  • Hepatocellular carcinoma (HCC) is the main type of adult liver cancer, the sixth most common cancer, and the third cause of cancer-related death worldwide. It most often occurs in a background of chronic inflammatory disease of the liver, mainly caused by hepatitis virus infection, excess lipid accumulation in Non-Alcoholic Fatty Liver Disease, or alcohol consumption. Under these settings, progressive fibrosis can lead to cirrhosis, considered irreversible and characterized by a distortion of the liver parenchyma and vascular architecture, and may ultimately result in HCC. Increasing evidence show that during carcinogenesis, the tumor cells and the TME, composed by stromal cells, fibroblasts, the extracellular matrix and importantly by immune cells such as tumor associated macrophages (TAMs), create a complex cellular system with reciprocal signaling that influences the tumor aggressiveness and outcome. Macrophages are very plastic cells that change their phenotype according to the microenvironment and it has been suggested that liver cancer cells may play a role in modulating macrophage activation state. Specifically in/around the tumor, macrophages may acquire M2-like properties resembling those of tolerant macrophages, promoting angiogenesis, metastasis and suppression of adaptive immunity. In line with this, in HCC, several studies correlate the presence of M2 TAMs with poor patient prognosis. In this thesis work, we aimed at analyzing the interplay between hepatocytes and macrophages in the setting of HCC. We have performed immunohistochemistry and immunofluorescence analysis of human tissue samples from HCC and surrounding cirrhotic tissue, and analyzed the interplay of liver cancer cells and macrophages in vitro with primary cells and cell lines. Our findings shed new light on the communication between macrophages and liver cancer cells and could be the basis for new therapeutic interventions.