Tumor regulation of the tissue environment in the liver.
The tumor microenvironment (TME) in the liver plays an important role in primary and metastatic liver tumor formation and tumor growth promotion. Cellular and non-cellular components of the TME significantly influence tumor development, growth, metastatic spread, anti-tumor immunity and response to tumor therapy. The cellular components of the TME in the liver not only consist of infiltrating immune cells, but also of liver-resident cells such as liver sinusoidal endothelial cells (LSEC) and hepatic stellate cells (HSC), which promote tumor growth by negatively regulating tumor-associated immune responses. In this review, we characterize cells of the TME with pro- and anti-tumor function in primary and metastatic liver tumors. Furthermore, we summarize mechanisms that permit growth of hepatic tumors despite the occurrence of spontaneous anti-tumor immune responses and how novel therapeutic approaches targeting the TME could unleash tumor-specific immune responses to improve survival of liver cancer patients.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Tobias
T
Eggert
Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: tim.greten@nih.gov.
Tim F
TF
Greten
D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D058990:Molecular Targeted Therapy; D015996:Survival Rate; D059016:Tumor Microenvironment
Hepatocellular carcinoma; Immunotherapy; Liver immunology; Liver metastases; Tumor immunology; Tumor microenvironment