Related Experiment Video

Updated: Jan 16, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.4K

NRF2 activation in cancer cells suppresses immune infiltration into the tumor microenvironment

Huaichun Wen1, Takafumi Suzuki1,2, Anqi Zhang1

  • 1Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Japan.

Iscience
|October 2, 2025
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (NRF2) activation in cancer cells suppresses immune cell infiltration into tumors. This finding reveals a mechanism linking NRF2 to cancer malignancy and immune evasion.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) hyperactivation in cancer is linked to immune suppression within the tumor microenvironment.
  • The direct impact of NRF2 hyperactivation on immune cell infiltration into tumors remains incompletely understood.

Purpose of the Study:

  • To investigate whether NRF2 hyperactivation directly reduces immune cell infiltration into tumors.
  • To elucidate the mechanistic link between NRF2 activation and immune suppression in cancer.

Main Methods:

  • Established a syngeneic mouse model using 3LL lung cancer cells.
  • Utilized Keap1 gene deletion for NRF2 hyperactivation and concomitant Keap1-Nrf2 gene deletion.
  • Employed flow cytometry, histological analysis, and gene expression profiling.

Main Results:

  • Keap1 deletion (NRF2 hyperactivation) significantly reduced immune cell infiltration in tumors, notably CD45-positive cells, myeloid, and monocytic populations.
  • Concomitant deletion of NRF2 in Keap1-deleted tumors restored immune cell infiltration.
  • NRF2 activation in cancer cells directly suppresses immune cell infiltration.

Conclusions:

  • NRF2 activation in cancer cells plays a direct role in suppressing immune cell infiltration.
  • This study provides mechanistic insights into how NRF2 contributes to cancer malignancy and immune evasion.
Keywords:
CancerImmunologyMolecular biology

More Related Videos

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports07:44

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports

Published on: November 28, 2019

8.0K
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells09:04

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

Published on: March 7, 2025

1.5K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
9.8K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.6K
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...
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.
1.8K
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...
5.1K
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...
9.4K