The tumor microenvironment of VETC+ hepatocellular carcinoma is enriched of immunosuppressive TAMs spatially close to endothelial cells.
Dig Liver Dis
; 2024 Jun 29.
Article
em En
| MEDLINE
| ID: mdl-38945759
ABSTRACT
BACKGROUND AND AIM:
VETC (vessel that encapsulate tumor cluster) is a peculiar vascular phenotype observed in hepatocellular carcinoma (HCC), associated with distant metastases and poor outcome. VETC has been linked to the Tie2/Ang2 axis and is characterized by lymphocytes poor (cold) tumor microenvironment (TME). In this setting the role of Tumor Associated Macrophages (TAMs) has never been explored. Aim of the study is to investigate the presence and features of TAMs in VETC+ HCC and the possible interplay between TAMs and endothelial cells (ECs).METHODS:
The series under study included 42 HCC. Once separated according to the VETC phenotype (21 VETC+; 21 VETC-) we stained consecutive slides with immunohistochemistry for CD68, CD163 and Tie2. Slides were then scanned and QuPath used to quantify morphological features.RESULTS:
VETC+ cases were significantly (p < 0.001) enriched with large, lipid rich CD163+ TAMs (M2 oriented) that were spatially close to ECs; HCC cells significantly (p 0.002) overexpressed Tie2 with a polarization toward ECs.CONCLUSIONS:
The pro-metastatic attitude of VETC is sustained by a strict morphological relationship between immunosuppressive M2-TAMs, ECs and Tie2-expressing HCC cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Dig Liver Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Itália
País de publicação:
Holanda