TY - JOUR T1 - Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-017-0285-7 VL - 5 IS - 1 SP - 81 AU - Daniel E. Carvajal-Hausdorf AU - Nikita Mani AU - Vamsidhar Velcheti AU - Kurt A. Schalper AU - David L. Rimm Y1 - 2017/12/01 UR - http://jitc.bmj.com/content/5/1/81.abstract N2 - Background Immunostimulatory therapies targeting immune-suppressive pathways produce durable responses in advanced solid tumors. Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting oxidoreductase that catalyzes the degradation of tryptophan to kynurenine. IDO induces immune tolerance by downregulating CD8+ and effector CD4+ T cell responses. IDO1, the most active isoform, is expressed in diverse tumor types and can be targeted using small molecule inhibitors. We used an objective, in situ assay to measure IDO1 in a collection of hormone receptor-positive breast cancers (HR+ BC).Methods IDO1 protein was measured using quantitative immunofluorescence in 362 stage I-III HR+ BC represented in tissue microarrays. IDO1 levels were determined in the tumor and stroma, and stratified using median cut-point. Associations between IDO1, clinico-pathological features and CD3+, CD8+, CD20+ and FOXP3 tumor-infiltrating lymphocytes were examined using χ2 and Mann-Whitney tests. Survival was studied using Kaplan-Meier estimator and a proportional hazards model. All tests were two-sided.Results IDO1 protein was observed in 76.2% of HR+ BC. There was no association between IDO1 and major clinico-pathological characteristics. Increased IDO1 correlated with decreased CD20+ infiltration (P = 0.0004) but not with CD3+, CD8+ or FOXP3 levels. Elevated IDO1 expression was associated with worse 20-year overall survival (log-rank P = 0.02, HR = 1.39, 95% C.I.: 1.05-1.82). IDO1 scores were independently associated with outcome in multivariable analysis.Conclusions IDO1 protein is expressed in the majority of HR+ BC and is an independent negative prognostic marker. Additionally, IDO1 expression is negatively associated with tumor B-cell infiltration. Measurement of IDO1 has the potential to identify a population that might derive benefit from IDO1 blockade.Abbreviations:DAPI4,6-diamidino-2-phenylindoleEDTAEthylenediaminetetraacetic acidEREstrogen receptorFFPEFormalin-fixed, paraffin-embeddedGCN2General control nonderepressible 2HR+ BCHormone receptor-positive breast cancerIDOIndoleamine 2,3 dioxygenaseIHCImmunohistochemistrymTORMammalian target of rapamacinNADNicotinamide adenine dinucleotideOSOverall survivalPD-1Program death 1PD-L1Program death ligand 1QIFQuantitative immunofluoresceR2Linear regression coefficientRNARibonucleic acidTILTumor-infiltrating lymphocytesTMATissue microarray ER -