Abstract

Abstract Purpose: Defects in human leukocyte antigen (HLA) class I antigen processing machinery (APM) component expression can have a negative impact on the clinical course of tumors and the response to T cell-based immunotherapy. Since brain metastases of breast cancer are of increasing clinical significance and only scant information is available about the expression of APM component abnormalities in these lesions, the APM component expression and CD8+ T cell infiltration pattern was analyzed in primary breast and metastatic brain lesions of breast cancer. Experimental design: Immunohistochemistry was performed to evaluate the expression of APM components HLA class I heavy chain, β2-microglobulin, tapasin, antigen peptide transporter (TAP)1, TAP2, LMP2 and calnexin. Results: Comparison of unpaired 50 primary and 33 brain metastases showed lower expression of β2-microglobulin, TAP1, TAP2 and calnexin in the brain lesions. Although no significant differences were found in APM component scores between primary breast and brain lesions in 15 paired cases, primary breast lesions of which patients eventually developed brain metastases showed lower levels of β2-microglobulin, TAP1 and calnexin compared with newly diagnosed breast lesions without brain metastases. Furthermore, the extent of CD8+ T cell infiltration was significantly higher in the newly diagnosed breast lesions compared with the ones of which the patients developed brain metastases, and was positively associated with the expression of TAP1 and calnexin. Conclusions: Our data suggest that patients with low or defective TAP1 or calnexin in the primary breast cancers may be at higher risks for developing brain metastases due to the reduced immunosurveillance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2439. doi:10.1158/1538-7445.AM2011-2439

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