Tumor steatosis and glutamine synthetase expression in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab therapy.

Autor: Kurebayashi Y; Department of Pathology, Keio University School of Medicine, Tokyo, Japan., Tsujikawa H; Department of Pathology, Keio University School of Medicine, Tokyo, Japan.; Department of Diagnostic Pathology, Keio University Hospital, Tokyo, Japan., Sugimoto K; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Yunaiyama D; Department of Radiology, Tokyo Medical University, Tokyo, Japan., Araki Y; Department of Radiology, Tokyo Medical University, Tokyo, Japan., Saito K; Department of Radiology, Tokyo Medical University, Tokyo, Japan., Takahashi H; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Kakegawa T; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Wada T; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Tomita Y; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Abe M; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Yoshimasu Y; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Takeuchi H; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Hirata T; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Sakamaki K; Center for Data Science, Yokohama City University, Yokohama, Japan., Kakimi K; Department of Immuno-therapeutics, The University of Tokyo Hospital, Tokyo, Japan., Nagao T; Department of Anatomical Pathology, Tokyo Medical University, Tokyo, Japan., Itoi T; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan., Sakamoto M; Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Hepatology research : the official journal of the Japan Society of Hepatology [Hepatol Res] 2023 Oct; Vol. 53 (10), pp. 1008-1020. Date of Electronic Publication: 2023 Jun 23.
DOI: 10.1111/hepr.13933
Abstrakt: Aim: The anti-programmed death-ligand 1 antibody atezolizumab and vascular endothelial growth factor-neutralizing antibody bevacizumab in combination (Atezo + Bev) have become the first-line therapy in advanced hepatocellular carcinoma (HCC). Distinct types of tumor immune microenvironment (TIME) and their associations with specific molecular subclasses and driver gene mutations have been identified in HCC; however, these insights are mainly based on surgically resected early-stage tumors. The current study aimed to reveal the biology and TIME of advanced HCC and their significance in predicting clinical outcomes of Atezo + Bev therapy.
Methods: Thirty-three patients with advanced HCC who were scheduled for treatment with Atezo + Bev therapy were included in this study. Pretreatment tumor biopsy, pre- and posttreatment diffusion-weighted magnetic resonance imaging (MRI) with nine b values (0-1500 s/mm 2 ), and other clinicopathologic factors were analyzed.
Results: Compared with resectable HCC, advanced HCC was characterized by higher proliferative activity, a higher frequency of Wnt/β-catenin-activated HCC, and lower lymphocytic infiltration. Prognostically, two metabolism-related factors, histopathologically determined tumor steatosis and/or glutamine synthetase (GS) expression, and MRI-determined tumor steatosis, were the most significant prognostic indicators for progression-free survival (PFS) and overall survival after Atezo + Bev therapy. Furthermore, changes in the pre- and posttreatment true diffusion coefficients on MRI, which might reflect changes in TIME after treatment, were significantly associated with better PFS.
Conclusions: The biology and TIME of HCC were strikingly different in advanced HCC compared with those of surgically resected HCC. Two metabolism-related factors, pathologically determined tumor steatosis and/or GS expression, and MRI-determined tumor steatosis, were found to be the most significant prognostic indicators for Atezo + Bev therapy in advanced HCC.
(© 2023 Japan Society of Hepatology.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje