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Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer
Abstract
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 tumor were 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 containing vimentin+ 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.
Authors
Jennifer R. Eng, Elmar Bucher, Zhi Hu, Cameron R. Walker, Tyler Risom, Michael Angelo, Paula Gonzalez-Ericsson, Melinda E. Sanders, A. Bapsi Chakravarthy, Jennifer A. Pietenpol, Summer L. Gibbs, Rosalie C. Sears, Koei Chin
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