Related Experiment Video

Updated: May 26, 2026

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
11:13

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity

Published on: July 12, 2018

PGK1 Suppresses CD8+ T Cell-Mediated Antitumor Immunity Through CCL2/CCR2/Tumor-Associated Macrophages Axis in

Xi Liu1,2,3,4, Jianpeng Liu1,2,3,4, Zhihao Zhang1,2,3,4

  • 1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|May 25, 2026
PubMed

Insights

Phosphoglycerate kinase 1 (PGK1) drives hepatocellular carcinoma (HCC) progression by suppressing CD8+ T cell immunity. Targeting PGK1 with combination immunotherapy shows promise for treating advanced HCC.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Advanced hepatocellular carcinoma (HCC) presents a poor prognosis with limited treatment options.
  • The tumor microenvironment in HCC is immunosuppressive, hindering immune checkpoint inhibitor efficacy.
  • The role of Phosphoglycerate kinase 1 (PGK1) in tumor immunity is not well understood.

Purpose of the Study:

  • To investigate the role of PGK1 in hepatocellular carcinoma (HCC) progression and tumor immunity.
  • To elucidate the mechanisms by which PGK1 influences the tumor microenvironment.
  • To evaluate the potential of targeting PGK1 in combination with immunotherapy for HCC treatment.

Main Methods:

  • In vivo and in vitro experiments were conducted to assess PGK1's function in HCC.
  • Investigated the interaction between PGK1, tumor-associated macrophages (TAMs), and CD8+ T cells.
  • Analyzed the role of C-C motif chemokine ligand 2 (CCL2) and its receptor CCR2 in PGK1-mediated immunosuppression.
  • Examined the involvement of the AKT/GSK3β/β-catenin pathway in PGK1-induced CCL2 secretion.

Main Results:

  • HCC cell-intrinsic PGK1 inhibits CD8+ T cell-mediated antitumor immunity.
  • PGK1 promotes TAM recruitment and M2 polarization via CCL2 upregulation.
  • CCL2 blockade reverses PGK1-induced immunosuppression and restores CD8+ T cell function.
  • PGK1 activates the AKT/GSK3β/β-catenin pathway, enhancing CCL2 secretion.
  • Combination of PGK1 inhibitor and immunotherapy demonstrated significant antitumor effects in vivo.

Conclusions:

  • PGK1 is a key regulator of tumor immunity in hepatocellular carcinoma (HCC).
  • PGK1 contributes to HCC progression by fostering an immunosuppressive microenvironment through TAMs and CCL2.
  • Targeting PGK1 offers a novel therapeutic strategy, particularly in combination with immunotherapy for advanced HCC.
Keywords:
CCL2CD8+ T cellPGK1hepatocellular carcinomatumor‐associated macrophages

More Related Videos

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity08:41

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity

Published on: June 7, 2017

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...
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...
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 daughter...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...