%0 Journal Article %A Sotirios P. Fortis %A Michael Sofopoulos %A Nectaria N. Sotiriadou %A Christoforos Haritos %A Christoforos K. Vaxevanis %A Eleftheria A. Anastasopoulou %A Nicole Janssen %A Niki Arnogiannaki %A Alexandros Ardavanis %A Graham Pawelec %A Sonia A. Perez %A Constantin N. Baxevanis %T Differential intratumoral distributions of CD8 and CD163 immune cells as prognostic biomarkers in breast cancer %D 2017 %R 10.1186/s40425-017-0240-7 %J Journal for ImmunoTherapy of Cancer %P 39 %V 5 %N 1 %X Background Tumor immune cell infiltrates are essential in hindering cancer progression and may complement the TNM classification. CD8+ and CD163+ cells have prognostic impact in breast cancer but their spatial heterogeneity has not been extensively explored in this type of cancer. Here, their potential as prognostic biomarkers was evaluated, depending on their combined densities in the tumor center (TC) and the tumor invasive margin (IM).Methods CD8+ and CD163+ cells were quantified by immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from a cohort totaling 162 patients with histologically-confirmed primary invasive non-metastatic ductal breast cancer diagnosed between 2000 and 2015. Clinical follow-up (median 6.9 years) was available for 97 of these patients.Results Differential densities of CD8+ and CD163+ cells in the combined TC and IM compartments (i.e., high(H)/low(L), respectively for CD8+ cells and the reverse L/H combination for CD163+ cells) were found to have significant prognostic value for survival, and allowed better patient stratification than TNM stage, tumor size, lymph node invasion and histological grade. The combined evaluation of CD8+ and CD163+ cell densities jointly in TC and IM further improves prediction of clinical outcomes based on disease-free and overall survival. Patients having the favorable immune signatures had favorable clinical outcomes despite poor clinicopathological parameters.Conclusions Given the important roles of CD8+ and CD163+ cells in regulating opposing immune circuits, adding an assessment of their differential densities to the prognostic biomarker armamentarium in breast cancer would be valuable. Larger validation studies are necessary to confirm these findings.Trial registrations Study code: IRB-ID 6079/448/10-6-13Date of approval: 10/06/2013Retrospective study (2000–2010)First patient prospectively enrolled 14/2/2014Abbreviations:BCaBreast cancerDCsDendritic cellsDFSDisease free survivalFCISFavorable combined immune signatureFFPEFormalin-fixed, paraffin-embeddedHEHematoxylin-eosinHRHazard ratioIL-2Interleukin-2IMInvasive marginiNKTInvariant natural killer TNKNatural killer cellOSOverall survivalTAMsTumor-associated macrophagesTCTumor centerTGFβTransforming growth factor betaTILsTumor-infiltrating lymphocytesUCISUnfavorable combined immune signature %U https://jitc.bmj.com/content/jitc/5/1/39.full.pdf