Cyclin G2 reverses immunosuppressive tumor microenvironment and potentiates PD-1 blockade in glioma

Sen Li1, Chenyang Zhao1, Jinlan Gao1

  • 1The Research Center for Medical Genomics, Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Science, China Medical University, No.77 Puhe Road, Shenyang North New Area, Liaoning Province, Shenyang, People's Republic of China.

Abstract

Insights

Cyclin G2 acts as a tumor suppressor in glioma by inhibiting proliferation and promoting apoptosis. It also enhances anti-tumor immunity and improves responses to PD-1 blockade immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Aberrant cyclin G2 expression is implicated in glioma development.
  • The role of cyclin G2 in the glioma tumor immune microenvironment is not well understood.

Purpose of the Study:

  • To elucidate the mechanism of cyclin G2 in regulating the glioma tumor immune microenvironment.
  • To investigate the biological functions of cyclin G2 in glioma progression and immunomodulation.

Main Methods:

  • Co-immunoprecipitation, in situ proximity ligation assay, and kinase assays were used to study cyclin G2's regulation of LDHA phosphorylation.
  • In vitro and in vivo experiments assessed cyclin G2's effects on glioma cell behavior and immune responses.
  • Immunohistochemistry was employed to examine cyclin G2 and Foxp3 expression in glioma specimens.

Main Results:

  • Cyclin G2 inhibits LDHA Y10 phosphorylation by impeding the LDHA-FGFR1 interaction.
  • Cyclin G2 suppresses glioma cell proliferation, migration, invasion, and glycolysis while promoting apoptosis.
  • Cyclin G2 reverses the immunosuppressive tumor microenvironment by reducing lactate production and enhances PD-1 blockade efficacy.

Conclusions:

  • Cyclin G2 functions as a tumor suppressor in glioma.
  • Cyclin G2 enhances glioma patient responses to immunotherapy, suggesting its potential as a predictive biomarker.

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...
5.1K
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.
771
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
36.7K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.8K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K