Abstract 462: Cytotoxic CD8+ T cells and immunosuppressive T regulatory cells are associated with aggressive breast cancer subtypes

Abstract

Abstract Background: An increase in tumor infiltrating lymphocytes (TILs) indicates an immune response to tumor antigens. CD8+ TILs play a vital role in cancer progression, and may have tumor suppressive effects. FoxP3+ T regulatory cells (Tregs), however, suppress a variety of immune cells - including CD4+ TILs, CD8+ TILs, dendritic cells, B cells, and macrophages - and thus may inhibit the beneficial effect these cells have on tumor suppression. Specifically, CD8+ TILs - which are a critical component of tumor-specific adaptive immunity - are a major target of Tregs. This study was aimed at understanding how these TILs correlate with breast cancer molecular subtypes in diverse population of breast cancer patients. Methods: Tissue Microarrays (TMAs) of breast cancer cases from 1992-2010 were obtained from the University of Chicago breast cancer biospecimen bank under IRB approved protocols. Molecular subtype was assigned based on immunohistochemical (IHC) staining into the following groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2-like (ER/PR-, HER2+) and basal-like (ER/PR/HER2-, EGFR+ and/or CK5/6+). IHC for CD8 and FoxP3 was performed on TMAs using DAKO, cat # M7103 antibody, and Abcam antibody cat #ab20034. The amount of CD8+ and FoxP3+ cells presents within the neoplastic tissue were counted manually in two high-powered fields (x400) by two independent pathologists, and recalculated for 1 mm2. The ratio of FoxP3+/CD8+ was calculated and correlated with molecular subtype. Results: Of the 292 cores evaluated, 268 were evaluable representing 134 individual cases. There were 28 basal-like (20.9%), 14 HER2 (10.4%), 78 luminal A (58.3%), and 14 luminal B (10.4%). Basal-like tumors showed the highest infiltration of both Tregs and CD8+ TILs when compared to other breast cancer subtypes, and the ratio of FoxP3+: CD8+ TILs in basal-like tumors were 1.7, 2.5, and 4.5-fold higher than in HER2, Luminal A, and Luminal B tumors respectively (p<0.05 for all correlations). Summary: FoxP3+ and CD8+ TIL infiltration density were significantly different among molecular subtypes of breast cancer. Future studies will examine the genomic determinants and prognostic significance of TILs in aggressive breast cancer subtypes, especially basal-like breast cancers. Citation Format: Galina F. Khramtsova, Rita Nanda, Ekaterina A. Khramtsova, Lise Sveen, Sope Olugbile, Olufunmilayo I. Olopade. Cytotoxic CD8+ T cells and immunosuppressive T regulatory cells are associated with aggressive breast cancer subtypes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 462. doi:10.1158/1538-7445.AM2015-462