Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer

Simple item page
dc.contributor.authorCarvajal, Daniel
dc.contributor.authorMani, Nikita
dc.contributor.authorVelcheti, Vamsidhar
dc.contributor.authorSchalper, Kurt
dc.contributor.authorRimm, David
dc.date.accessioned2018-01-15T13:53:11Z
dc.date.available2018-01-15T13:53:11Z
dc.date.issued2017
dc.description.abstractBACKGROUND: 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.
dc.format.extent9
dc.identifier.citationJ Immunother Cancer. 2017 Oct 17;5(1):81
dc.identifier.urihttp://hdl.handle.net/11447/1898
dc.identifier.urihttp://dx.doi.org/10.1186/s40425-017-0285-7
dc.language.isoen_US
dc.publisherBioMed Central
dc.subjectHormone receptor-positive
dc.subjectIDO1
dc.subjectQuantitative immunofluorescence
dc.subjectSurvival
dc.subjectTumor-infiltrating lymphocytes
dc.titleObjective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer
dc.typeArtículo

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer____completo.pdf
Size:
1.98 MB
Format:
Adobe Portable Document Format
Description:
Texto completo
Download

Collections

Artículos Medicina y Ciencias de la Salud

Implementado por OpenGeek Services