Emergence of immune escape variant of mammary tumors that has distinct proteomic profile and a reduced ability to induce "danger signals"

Masoud H. Manjili, Hilal Arnouk, Keith L. Knutson, Maciej Kmieciak, Mary L. Disis, John R. Subjeck, A. Latif Kazim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Breast tumors are shaped, in part, by a process termed immunoediting which selects for immunologically evasive phenotypes. In the present study we used the rat neu-transgenic mouse model of breast cancer and its congenic non-transgenic parental strain, FVB, to explore the phenotype of tumors that emerge in the presence of an immune response directed against the neu antigen. When inoculated into parental FVB mice, a neu-overexpressing mouse mammary carcinoma (MMC) cell line isolated from spontaneous breast tumors of the FVB neu (FVBN202) transgenic mouse, elicited a neu-specific immune response resulting in a tumor rejection because of the presence of the rat neu antigen. However, a neu negative variant (ANV) of MMC arose after a long latency in spite of the neu-specific immune response. We show that compared to MMC, ANV tumor cells have a significantly reduced ability to secrete pro-inflammatory cytokines and the CCL5 chemokine, to express immunostimulatory chaperones, and they have a distinct expression of proteins involved in cell motility, and metabolic and signal transduction pathways. These studies suggest that tumor escape through immunoediting can not be explained by the loss of a single tumor antigen, but rather by a selection process of a tumor variant that has a reduced ability to induce "danger signals" together with up-regulation of proteins involved in the tumor survival. Based on these findings, we propose to target novel antigens over-expressed in the escape variant of breast tumors to treat primary tumor and to prevent tumor relapse.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - Apr 2006


  • Breast cancer
  • Danger signal
  • HER-2/neu
  • Heat shock proteins
  • Tumor escape

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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