Related Experiment Video

Updated: Jun 17, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
00:06

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

8.8K

Anti-CTLA-4 treatment suppresses hepatocellular carcinoma growth through Th1-mediated cell cycle arrest and apoptosis

Hitomi Morihara1,2, Tomomi Yamada2, Yumi Tona2

  • 1Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.

Plos One
|August 6, 2024
PubMed

Insights

Anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody therapy suppresses cancer by activating T-helper 1 (Th1) cells. These Th1 cells release interferon-gamma (IFN-g), inducing tumor cell cycle arrest and apoptosis.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Biology

Background:

  • Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is a key immune checkpoint target for cancer immunotherapy.
  • The precise mechanisms by which anti-CTLA-4 antibodies exert anti-tumor effects remain incompletely understood.

Purpose of the Study:

  • To elucidate the mechanisms of anti-CTLA-4 antibody-mediated tumor suppression in hepatocellular carcinoma.
  • To investigate the roles of specific T cell subsets and cytokines in anti-CTLA-4 therapy.

Main Methods:

  • Establishment of a monoclonal hepatocellular carcinoma cell line (Hepa1-6 #12).
  • Analysis of T cell populations (CD4+, CD8+) within tumors following anti-CTLA-4 antibody treatment.
  • Interferon-gamma (IFN-g) neutralization experiments.
  • In vitro assessment of IFN-g's effects on tumor cells.

Main Results:

  • Anti-CTLA-4 antibody efficacy was dependent on CD4+ T cells, not CD8+ T cells.
  • Treatment led to the recruitment of IFN-g-producing T-helper 1 (Th1) cells into tumors.
  • Neutralization of IFN-g abolished the anti-tumor activity.
  • IFN-g induced cell cycle arrest and apoptosis in tumor cells independently of MHC expression.

Conclusions:

  • Anti-CTLA-4 antibody therapy promotes anti-tumor immunity through Th1 cell recruitment and IFN-g production.
  • The mechanism involves IFN-g-induced tumor cell cycle arrest and apoptosis.
  • This study highlights the critical role of the Th1-IFN-g axis in anti-CTLA-4 immunotherapy.

More Related Videos

Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice07:25

Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice

Published on: September 25, 2019

6.8K
Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

18.7K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
497
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.5K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
124