Related Experiment Video

Updated: Jan 26, 2026

Orthotopic Mouse Model of Colorectal Cancer
08:43

Orthotopic Mouse Model of Colorectal Cancer

Published on: December 4, 2007

47.1K

Oncogenic KRAS Drives Immune Suppression in Colorectal Cancer

Kay Hänggi1, Brian Ruffell2

  • 1Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.

Cancer Cell
|April 17, 2019
PubMed

Insights

Oncogenic KRAS in colorectal cancer represses IRF2, suppressing the immune response and causing resistance to immune checkpoint blockade therapy. This study reveals a novel immune suppressive mechanism driven by KRAS.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) is a major global health challenge.
  • Immune checkpoint blockade (ICB) therapy has shown promise in CRC but resistance remains a significant issue.
  • The role of KRAS mutations in modulating the tumor immune microenvironment is not fully understood.

Purpose of the Study:

  • To investigate the mechanisms by which oncogenic KRAS influences the immune suppressive program in colorectal cancer.
  • To elucidate the downstream effects of KRAS-mediated repression of IRF2 on immune cell infiltration and response to ICB.

Main Methods:

  • Analysis of patient-derived colorectal cancer samples.
  • In vitro cell line experiments.
  • In vivo mouse models of colorectal cancer.

Main Results:

  • Oncogenic KRAS was found to repress Interferon Regulatory Factor 2 (IRF2) expression in colorectal cancer cells.
  • Repression of IRF2 led to the downregulation of interferon-responsive genes.
  • This resulted in enhanced expression of CXCL3, recruitment of suppressive myeloid cells, and resistance to immune checkpoint blockade.

Conclusions:

  • Oncogenic KRAS actively drives an immune suppressive program in colorectal cancer by inhibiting IRF2.
  • This KRAS-driven pathway contributes to therapeutic resistance against immune checkpoint blockade.
  • Targeting this pathway may represent a novel strategy to overcome ICB resistance in colorectal cancer.

More Related Videos

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer06:01

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Published on: July 6, 2017

9.9K
Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer06:49

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer

Published on: February 10, 2023

2.7K

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

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...
11.2K
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
2.7K
What is the Immune System?01:38

What is the Immune System?

Overview
127.3K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.4K
Humoral Immune Responses01:36

Humoral Immune Responses

Overview
83.5K
Acid Suppressive Drugs for Peptic Ulcer Disease: Antacids01:31

Acid Suppressive Drugs for Peptic Ulcer Disease: Antacids

In the complex environment of the gastric lumen, excessive acid secretion can lead to the formation or worsening of ulcers within the delicate mucosal layer. Antacids, such as sodium bicarbonate and calcium carbonate, provide relief by neutralizing this acid, transforming it into harmless salt and water. This neutralization process raises the gastric pH from a highly acidic level of 1 to a more basic 3-4, reducing the acidity within the stomach.
However, this neutralization reaction between...
656