Role of β-Catenin Activation in the Tumor Immune Microenvironment and Immunotherapy of Hepatocellular Carcinoma.

hepatocellular carcinoma immune checkpoint inhibitor immune microenvironment molecular target agent β-catenin activation

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
15 Apr 2023
Historique:
received: 25 02 2023
revised: 09 04 2023
accepted: 13 04 2023
medline: 16 5 2023
pubmed: 16 5 2023
entrez: 16 5 2023
Statut: epublish

Résumé

Recently, the therapeutic combination of atezolizumab and bevacizumab was widely used to treat advanced hepatocellular carcinoma (HCC). According to recent clinical trials, immune checkpoint inhibitors (ICIs) and molecular target agents are expected to be key therapeutic strategies in the future. Nonetheless, the mechanisms underlying molecular immune responses and immune evasion remain unclear. The tumor immune microenvironment plays a vital role in HCC progression. The infiltration of CD8-positive cells into tumors and the expression of immune checkpoint molecules are key factors in this immune microenvironment. Specifically, Wnt/β catenin pathway activation causes "immune exclusion", associated with poor infiltration of CD8-positive cells. Some clinical studies suggested an association between ICI resistance and β-catenin activation in HCC. Additionally, several subclassifications of the tumor immune microenvironment were proposed. The HCC immune microenvironment can be broadly divided into inflamed class and non-inflamed class, with several subclasses. β-catenin mutations are important factors in immune subclasses; this may be useful when considering therapeutic strategies as β-catenin activation may serve as a biomarker for ICI. Various types of β-catenin modulators were developed. Several kinases may also be involved in the β-catenin pathway. Therefore, combinations of β-catenin modulators, kinase inhibitors, and ICIs may exert synergistic effects.

Identifiants

pubmed: 37190239
pii: cancers15082311
doi: 10.3390/cancers15082311
pmc: PMC10136695
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

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Auteurs

Masahiro Morita (M)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Naoshi Nishida (N)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Tomoko Aoki (T)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Hirokazu Chishina (H)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Masahiro Takita (M)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Hiroshi Ida (H)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Satoru Hagiwara (S)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Yasunori Minami (Y)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Kazuomi Ueshima (K)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Masatoshi Kudo (M)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

Classifications MeSH