Anti-CTLA-4 treatment suppresses hepatocellular carcinoma growth through Th1-mediated cell cycle arrest and apoptosis.
Carcinoma, Hepatocellular
/ drug therapy
Apoptosis
/ drug effects
Animals
Th1 Cells
/ immunology
CTLA-4 Antigen
/ antagonists & inhibitors
Liver Neoplasms
/ drug therapy
Cell Cycle Checkpoints
/ drug effects
Mice
Cell Line, Tumor
Interferon-gamma
/ metabolism
Humans
Mice, Inbred C57BL
Cell Proliferation
/ drug effects
Antibodies, Monoclonal
/ pharmacology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2024
2024
Historique:
received:
21
01
2024
accepted:
09
06
2024
medline:
6
8
2024
pubmed:
6
8
2024
entrez:
6
8
2024
Statut:
epublish
Résumé
Inhibiting the cytotoxic T-lymphocyte-associated protein-4 (CTLA-4)-mediated immune checkpoint system using an anti-CTLA-4 antibody (Ab) can suppress the growth of various cancers, but the detailed mechanisms are unclear. In this study, we established a monoclonal hepatocellular carcinoma cell line (Hepa1-6 #12) and analyzed the mechanisms associated with anti-CTLA-4 Ab treatment. Depletion of CD4+ T cells, but not CD8+ T cells, prevented anti-CTLA-4 Ab-mediated anti-tumor effects, suggesting dependence on CD4+ T cells. Anti-CTLA-4 Ab treatment resulted in recruitment of interferon-gamma (IFN-g)-producing CD4+ T cells, called T-helper 1 (Th1), into tumors, and neutralization of IFN-g abrogated the anti-tumor effects. Moreover, tumor growth suppression did not require major histocompatibility complex (MHC)-I or MHC-II expression on cancer cells. In vitro studies showed that IFN-g can induce cell cycle arrest and apoptosis in tumor cells. Taken together, these data demonstrate that anti-CTLA-4 Ab can exert its anti-tumor effects through Th1-mediated cell cycle arrest and apoptosis.
Identifiants
pubmed: 39106430
doi: 10.1371/journal.pone.0305984
pii: PONE-D-24-02816
doi:
Substances chimiques
CTLA-4 Antigen
0
Interferon-gamma
82115-62-6
Antibodies, Monoclonal
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0305984Informations de copyright
Copyright: © 2024 Morihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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