Immunoediting of cancers may lead to epithelial to mesenchymal transition.
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.
Knutson
Keith L
KL
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA. knutson.keith@mayo.edu
Lu
Hailing
H
Stone
Brad
B
Reiman
Jennifer M
JM
Behrens
Marshall D
MD
Prosperi
Christine M
CM
Gad
Ekram A
EA
Smorlesi
Arianna
A
Disis
Mary L
ML
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology*; D014644:Genetic Variation; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008648:Mesoderm / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000276:immunology; D009368:Neoplasm Transplantation / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology
D018719:Erb-b2 Receptor Tyrosine Kinases