Related Experiment Video

Updated: Jul 2, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.5K

PRMT1 acts as a suppressor of MHC-I and anti-tumor immunity

Tirta M Djajawi1, Lizzy Pijpers2, Akash Srivaths1

  • 1Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Melbourne, VIC 3086, Australia.

Cell Reports
|February 24, 2024
PubMed

Insights

Protein arginine methyltransferase 1 (PRMT1) limits cancer immunity by suppressing T-cell killing. Inhibiting PRMT1 enhances immunotherapy effectiveness and may offer new treatment strategies for cancer patients.

Area of Science:

  • Immunology
  • Epigenetics
  • Cancer Biology

Background:

  • Cancer immunotherapies show promise but face challenges with patient response and resistance.
  • Identifying epigenetic regulators of anti-tumor immunity is crucial for improving treatment efficacy.

Purpose of the Study:

  • To identify epigenomic factors limiting CD8+ T cell-mediated anti-tumor immunity using CRISPR-Cas9 screens.
  • To investigate the role of PRMT1 in regulating anti-tumor immune responses and its potential as a therapeutic target.

Main Methods:

  • Epigenetic gene-targeted CRISPR-Cas9 screens were employed to identify key regulators.
  • PRMT1 knockout and pharmacological inhibition (GSK3368715) were used to assess its function.
  • STAT1 expression and activation were analyzed to understand the mechanism of PRMT1 action.
  • The Cancer Genome Atlas (TCGA) database was utilized for correlative analysis in human melanoma.

Main Results:

  • PRMT1 was identified as a suppressor of interferon gamma (Ifnγ)-induced MHC-I expression, thereby impairing CD8+ T cell killing.
  • PRMT1 inhibition enhanced Ifnγ-induced MHC-I expression via increased STAT1 signaling.
  • Loss of PRMT1 improved the efficacy of anti-PD-1 immunotherapy in preclinical models.
  • TCGA analysis showed an inverse correlation between PRMT1 expression and immune markers (MHC-I, CD8+ T cells) and survival in melanoma patients.

Conclusions:

  • PRMT1 acts as a negative regulator of anti-tumor immunity by modulating MHC-I expression and T cell-mediated cytotoxicity.
  • Targeting PRMT1, particularly with type I PRMT inhibitors like GSK3368715, represents a promising strategy to enhance cancer immunotherapy.
  • PRMT1 inhibitors could be used as standalone treatments or in combination with existing immunotherapies to overcome resistance and improve patient outcomes.
Keywords:
CP: CancerCP: ImmunologyPRMT1STAT1argenine methylationcancerimmunology

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

8.2K
Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells08:11

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells

Published on: August 7, 2021

4.2K

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
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
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
21.3K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
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.
524