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Updated: Aug 7, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Immunoediting of cancers may lead to epithelial to mesenchymal transition
Keith L Knutson1, Hailing Lu, Brad Stone
1Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA. knutson.keith@mayo.edu
Abstract:
Tumors evade both natural and pharmacologically induced (e.g., vaccines) immunity by a variety of mechanisms, including induction of tolerance and immunoediting. Immunoediting results in reshaping the immunogenicity of the tumor, which can be accompanied by loss of Ag expression and MHC molecules. In this study, we evaluated immunoediting in the neu-transgenic mouse model of breast cancer. A tumor cell line that retained expression of rat neu was generated from a spontaneous tumor of the neu-transgenic mouse and, when injected into the non-transgenic parental FVB/N mouse, resulted in the development of a strong immune response, initial rejection, and ultimately the emergence of neu Ag-loss variants. Morphologic and microarray data revealed that the immunoedited tumor cells underwent epithelial to mesenchymal transition accompanied by an up-regulation of invasion factors and increased invasiveness characteristic of mesenchymal tumor cells. These results suggest that immunoediting of tumor results in cellular reprogramming may be accompanied by alterations in tumor characteristics including increased invasive potential. Understanding the mechanisms by which tumors are immunoedited will likely lead to a better understanding of how tumors evade immune detection.
Insights
Tumors can evade immune detection through immunoediting, where cancer cells lose antigen expression and undergo epithelial-to-mesenchymal transition, increasing their invasiveness.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Tumors employ various mechanisms, including immunoediting, to evade immune system detection and destruction.
- Immunoediting can lead to changes in tumor immunogenicity, such as loss of antigen (Ag) expression and MHC molecules.
Purpose of the Study:
- To investigate the process of immunoediting in a neu-transgenic mouse model of breast cancer.
- To analyze the cellular and molecular changes in tumor cells following immune-mediated selection.
Main Methods:
- Generated a tumor cell line expressing rat neu from a spontaneous tumor in neu-transgenic mice.
- Injected tumor cells into FVB/N mice to study immune response, tumor rejection, and emergence of variants.
- Utilized morphologic analysis and microarray data to assess cellular changes and gene expression.
Main Results:
- Injected tumor cells elicited a strong immune response and initial rejection in FVB/N mice.
- Emergence of tumor variants with loss of neu antigen expression was observed.
- Immunoedited tumor cells exhibited epithelial-to-mesenchymal transition, increased invasion factors, and enhanced invasiveness.
Conclusions:
- Tumor immunoediting can lead to cellular reprogramming, altering tumor characteristics such as invasive potential.
- Understanding immunoediting mechanisms is crucial for developing strategies to overcome tumor immune evasion.
- The neu-transgenic mouse model provides insights into breast cancer immunoediting and immune evasion strategies.
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