Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer

被引：2

作者：

Eng, Jennifer R. ^{[1
,2
]}

Bucher, Elmar ^{[2
]}

Hu, Zhi ^{[2
]}

Walker, Cameron R. ^{[3
]}

Risom, Tyler ^{[4
]}

Angelo, Michael ^{[3
]}

Gonzalez-Ericsson, Paula ^{[5
]}

Sanders, Melinda E. ^{[5
,6
]}

Chakravarthy, A. Bapsi

Pietenpol, Jennifer A. ^{[5
,7
]}

Gibbs, Summer L. ^{[2
]}

Sears, Rosalie C. ^{[1
]}

Chin, Koei ^{[8
]}

机构：

[1] Oregon Hlth & Sci Univ OHSU, Dept Mol & Med Genet, Portland, OR USA

[2] Oregon Hlth & Sci Univ OHSU, Dept Biomed Engn, Portland, OR USA

[3] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA USA

[4] Genentech Inc, Dept Res Pathol, South San Francisco, CA USA

[5] Vanderbilt Univ, Med Ctr VUMC, Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[6] Vanderbilt Univ Med Ctr VUMC, Dept Pathol Microbiol & Immunol, Nashville, TN USA

[7] Vanderbilt Univ, Dept Biochem, Nashville, TN USA

[8] OHSU, Canc Early Detect Adv Res Ctr, Portland, OR USA

来源：

JCI INSIGHT | 2025年 / 10卷 / 03期

关键词：

IMMUNOTHERAPY; ANGIOGENESIS; LANDSCAPE;

D O I：

10.1172/jci.insight.176749

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell spatial data from 3 multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 patients with breast cancer with clinical follow-up as well as publicly available mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among patients who are estrogen- receptor+ (ER+). We utilized discovery and validation cohorts to identify biomarkers with prognostic value. Increased lymphocyte infiltration was independently associated with longer survival in triple- negative (TN) and high-proliferation ER+ breast tumors. An assessment of 10 spatial analysis methods revealed robust spatial biomarkers. In ER+ disease, quiescent stromal cells close to tumorwere abundant in tumors with good prognoses, while tumor cell neighborhoods containing mixed fibroblast phenotypes were enriched in poor-prognosis tumors. In TN disease, macrophage/tumor and B/T lymphocyte neighbors were enriched, and lymphocytes were dispersed in good-prognosis tumors, while tumor cell neighborhoods containingvimentin+ fibroblasts were enriched in poor-prognosis tumors. In conclusion, we generated comparable single-cell spatial proteomic data from several clinical cohorts to enable prognostic spatial biomarker identification and validation.

引用

页数：21

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