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

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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