Immunoediting of cancers may lead to epithelial to mesenchymal transition

Keith L. Knutson, Hailing Lu, Brad Stone, Jennifer M. Reiman, Marshall D. Behrens, Christine M. Prosperi, Ekram A. Gad, Arianna Smorlesi, Mary L. Disis

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1526-1533
Number of pages8
JournalJournal of Immunology
Volume177
Issue number3
DOIs
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Immunoediting of cancers may lead to epithelial to mesenchymal transition'. Together they form a unique fingerprint.

Cite this