Potential involvement of oncostatin M in the immunosuppressive tumor immune microenvironment in hepatocellular carcinoma with vessels encapsulating tumor clusters.
hepatocellular carcinoma
oncostatin M
tumor-infiltrating immune cells
vessels encapsulating tumor clusters
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
10 Nov 2023
10 Nov 2023
Historique:
revised:
23
10
2023
received:
03
08
2023
accepted:
03
11
2023
pubmed:
11
11
2023
medline:
11
11
2023
entrez:
11
11
2023
Statut:
aheadofprint
Résumé
Vessels encapsulating tumor clusters (VETC) represents an adverse prognostic morphological feature of hepatocellular carcinoma (HCC), which is associated with an immunosuppressive tumor immune microenvironment (TIM). However, the underlying factors characterizing the TIM in HCC with a VETC pattern (VETC-positive HCC) remain uncertain. Oncostatin M (OSM), a pleiotropic cytokine of the interleukin-6 family, regulates various biological processes, including inflammation, proliferation, and invasiveness of tumor cells. We aimed to test a hypothesis that OSM is associated with the immunosuppressive TIM of VETC-positive HCC. A total of 397 consecutive HCC patients with curative-intent hepatectomy were included. OSM-positive cells and inflammatory cells including CD4-, CD8-, CD163-, and FOXP3-positive cells were immunohistochemically evaluated. We compared VETC-positive and VETC-negative HCCs in terms of the number of these cells. We found the VETC pattern in 62 patients (15.6%). Our analysis revealed a significant decrease in the expression of arginase-1, a marker associated with mature hepatocyte differentiation, in VETC-positive HCC (p = 0.046). The number of tumor-infiltrating OSM-positive cells was significantly low in VETC-positive HCC (p = 0.0057). Notably, in VETC-positive HCC, the number of OSM-positive cells was not associated with vascular invasion, whereas in VETC-negative HCC, an increase in the number of OSM-positive cells was associated with vascular invasion (p = 0.042). We identified an association between a decrease in OSM-positive cells and the VETC pattern. Additionally, our findings indicate that VETC-positive HCC is characterized by low hepatocyte differentiation and OSM-independent vascular invasion. These findings highlight the potential interaction between VETC-positive HCC cells and their TIM through the reduction of OSM-expressing cells.
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : JSPS KAKENHI
ID : JP22H02930
Organisme : JSPS KAKENHI
ID : JP23K18246
Organisme : JSPS KAKENHI
ID : JP23K14491
Informations de copyright
© 2023 Japan Society of Hepatology.
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