Related Experiment Video

Updated: Aug 7, 2025

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
09:32

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells

Published on: February 8, 2018

14.7K

Disrupting the phase separation of KAT8-IRF1 diminishes PD-L1 expression and promotes antitumor immunity

Yuanzhong Wu1, Liwen Zhou1, Yezi Zou1

  • 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Nature Cancer
|March 9, 2023
PubMed

Insights

New research reveals how interferon-γ (IFNγ) triggers KAT8 and IRF1 to form condensates, boosting PD-L1. A novel peptide disrupts this, inhibiting PD-L1 and enhancing anti-tumor immunity.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cancer Research

Background:

  • PD-1/PD-L1 axis immunotherapies are crucial cancer treatments.
  • Limited patient benefits highlight the need to understand PD-1/PD-L1 regulation mechanisms.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating PD-1/PD-L1 expression.
  • To identify novel therapeutic targets for enhancing anti-tumor immunity.

Main Methods:

  • Investigated the role of KAT8 and IRF1 in PD-L1 regulation using cellular assays.
  • Utilized biochemical and biophysical techniques to study biomolecular condensate formation.
  • Developed and tested a blocking peptide (2142-R8) for its efficacy in vitro and in vivo.

Main Results:

  • Interferon-γ (IFNγ) induces KAT8-IRF1 phase separation, forming biomolecular condensates that upregulate PD-L1.
  • Multivalent interactions between KAT8 and IRF1 are essential for condensate formation.
  • KAT8-IRF1 condensation enhances PD-L1 transcription by promoting IRF1 acetylation and promoter binding.
  • The 2142-R8 peptide disrupts KAT8-IRF1 condensates, inhibiting PD-L1 expression and improving anti-tumor immunity.

Conclusions:

  • KAT8-IRF1 biomolecular condensates play a critical role in regulating PD-L1 expression.
  • The identified peptide offers a potential therapeutic strategy to enhance anti-tumor immune responses by targeting PD-L1 upregulation.

More Related Videos

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

468
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood06:07

Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood

Published on: February 5, 2020

5.8K

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...
6.4K
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...
4.6K
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.
606
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