Related Experiment Video

Updated: Jul 3, 2025

Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
07:32

Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis

Published on: April 12, 2024

1.3K

HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and

Yi Zhang1, Mingjie Wang1,2, Ling Ye3

  • 1School of Medicine, South China University of Technology, Guangzhou, China.

Nature Communications
|February 13, 2024
PubMed

Insights

Hexokinase domain component 1 (HKDC1) drives tumor immune evasion by activating STAT1/PD-L1. Inhibiting HKDC1 enhances anti-tumor T cell responses, offering a new strategy for cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Immune checkpoint blockade (ICB) therapy shows promise for cancer treatment but benefits only a subset of patients due to immune evasion.
  • Mechanisms of tumor immune evasion and regulation of immune cell responses are not fully understood.

Purpose of the Study:

  • To investigate the role of hexokinase domain component 1 (HKDC1) in tumor immune evasion.
  • To elucidate the molecular mechanisms by which HKDC1 influences anti-tumor immunity.

Main Methods:

  • Investigated HKDC1's role in tumor immune evasion in CD8+ T cell-dependent manner.
  • Examined HKDC1's mechanism involving STAT1/PD-L1 activation in tumor cells.
  • Utilized liver cancer models in male mice and clinical hepatocellular carcinoma samples.

Main Results:

  • HKDC1 promotes tumor immune evasion by activating STAT1/PD-L1.
  • HKDC1 binds to cytosolic STAT1 and facilitates its phosphorylation and nuclear translocation via ACTA2.
  • Combination of HKDC1 inhibition with anti-PD-1/PD-L1 therapy enhanced in vivo T cell antitumor response.
  • Clinical data showed correlation between HKDC1 expression, STAT1 phosphorylation, and patient survival in hepatocellular carcinoma treated with atezolizumab.

Conclusions:

  • HKDC1 plays a critical role in regulating tumor immune evasion by linking the cytoskeleton to STAT1 activation.
  • Targeting HKDC1 in combination with ICB represents a potential strategy to improve anti-tumor immune responses and patient outcomes.

More Related Videos

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis00:06

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

Published on: September 12, 2019

8.9K
Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts07:18

Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts

Published on: June 13, 2019

6.9K

Related Concept Videos

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...
6.3K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.9K
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...
4.5K
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...
4.8K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.6K