Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure

Maciej Kmieciak, Kyle K. Payne, Michael O. Idowu, Margaret M. Grimes, Laura Graham, Maria Libera Ascierto, Ena Wang, Xiang Yang Wang, Harry D. Bear, Masoud H. Manjili

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Abstract

Background: Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure.Methods: We conducted a pilot study in patients with HER-2/neu positive and HER-2/neu negative breast cancers as well as a patient with ductal carcinoma in situ (DCIS). HER-2/neu expression was determined by FISH. HER-2/neu-specific T cell responses were determined by using IFN-γ ELISA. Expression of IFN-γ Rα in the tumors was determined by immunohistochemistry analysis of paraffin-embedded tissues.Results: We determined that majority of (10 of 12) patients with HER-2/neu negative breast cancer had HER-2/neu-specific IFN-γ producing T cell responses which was stronger than those in patients with HER-2/neu positive tumors. Such immune responses were associated with nuclear translocation of IFN-γ Rα in their tumor cells. Patient with DCIS also showed HER-2/neu-specific T cell responses.Conclusion: These data suggest that conducting retrospective studies in patients with HER-2/neu negative breast cancers and prospective studies in patients with HER-2/neu positive DCIS can determine whether HER-2/neu negative invasive carcinomas arise from HER-2/neu positive DCIS under the immune pressure.

Original languageEnglish
Article number35
JournalJournal of Translational Medicine
Volume9
DOIs
Publication statusPublished - 31 Mar 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kmieciak, M., Payne, K. K., Idowu, M. O., Grimes, M. M., Graham, L., Ascierto, M. L., Wang, E., Wang, X. Y., Bear, H. D., & Manjili, M. H. (2011). Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure. Journal of Translational Medicine, 9, [35]. https://doi.org/10.1186/1479-5876-9-35