Tumor escape and progression of HER-2-neu negative breast cancer under immune pressureReport as inadecuate




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Journal of Translational Medicine

, 9:35

First Online: 31 March 2011Received: 02 March 2011Accepted: 31 March 2011DOI: 10.1186-1479-5876-9-35

Cite this article as: Kmieciak, M., Payne, K.K., Idowu, M.O. et al. J Transl Med 2011 9: 35. doi:10.1186-1479-5876-9-35

Abstract

BackgroundEmerging 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.

MethodsWe 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.

ResultsWe 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.

ConclusionThese 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-9-35 contains supplementary material, which is available to authorized users.

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Author: Maciej Kmieciak - Kyle K Payne - Michael O Idowu - Margaret M Grimes - Laura Graham - Maria-Libera Ascierto - Ena Wang -

Source: https://link.springer.com/







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