Related Experiment Video

Updated: Jun 17, 2025

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
09:15

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

3.4K

Targeting p97-Npl4 interaction inhibits tumor Treg cell development to enhance tumor immunity

Pingping Nie1,2, Zhifa Cao2, Ruixian Yu1

  • 1State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.

Nature Immunology
|August 6, 2024
PubMed

Insights

Thonzonium bromide inhibits the p97-Npl4 complex, crucial for tumor-infiltrating regulatory T cells. This drug boosts anti-tumor immunity by affecting Treg-TH17 balance, offering a new immunotherapy target.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Regulatory T (Treg) cells within tumors suppress anti-cancer immune responses.
  • The ATPase p97, complexed with cofactors like Npl4, is a known anti-tumor target, but its role in immune cells was unclear.
  • Understanding p97's function in Treg cells is vital for developing novel cancer immunotherapies.

Purpose of the Study:

  • To investigate the role of the p97-Npl4 complex in tumor-infiltrating regulatory T (TI-Treg) cells.
  • To determine if targeting the p97-Npl4 interaction can enhance anti-tumor immunity.
  • To identify the molecular mechanisms by which the p97-Npl4 complex regulates TI-Treg cell function.

Main Methods:

  • Utilized thonzonium bromide as a specific inhibitor of the p97-Npl4 interaction.
  • Assessed the impact of p97-Npl4 inhibition on TI-Treg cell development and function.
  • Investigated the molecular bridging role of the p97-Npl4 complex involving Stat3 and E3 ligases (PDLIM2, PDLIM5).

Main Results:

  • Thonzonium bromide effectively inhibits the p97-Npl4 complex, which is critical for TI-Treg cell function.
  • Inhibition of the p97-Npl4 complex boosts anti-tumor immunity without disrupting peripheral Treg cell homeostasis.
  • The p97-Npl4 complex links Stat3 to PDLIM2/5, promoting Stat3 degradation and facilitating TI-Treg cell development.

Conclusions:

  • The p97-Npl4 complex plays a significant role in maintaining the balance between Treg and TH17 cells within the tumor microenvironment.
  • Targeting the p97-Npl4 interaction with inhibitors like thonzonium bromide represents a promising strategy for cancer immunotherapy.
  • This study identifies the p97-Npl4 complex as a key regulator of TI-Treg cells and a potential therapeutic target.

More Related Videos

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer07:55

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer

Published on: January 17, 2025

690
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells09:01

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

308

Related Concept Videos

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
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
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.7K
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...
7.3K
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...
6.2K
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