Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study

作者：H. Raza Ali, Leon Chlon, Paul D.P. Pharoah, Florian Markowetz, Carlos H. Caldas · 发表于：PLoS Medicine · 年份：2016 · DOI：10.1371/journal.pmed.1002194 · 被引用次数：683 · 研究领域：Cancer Immunotherapy and Biomarkers、Breast Cancer Treatment Studies、Immune cells in cancer

BACKGROUND: Immune infiltration of breast tumours is associated with clinical outcome. However, past work has not accounted for the diversity of functionally distinct cell types that make up the immune response. The aim of this study was to determine whether differences in the cellular composition of the immune infiltrate in breast tumours influence survival and treatment response, and whether these effects differ by molecular subtype. METHODS AND FINDINGS: We applied an established computational approach (CIBERSORT) to bulk gene expression profiles of almost 11,000 tumours to infer the proportions of 22 subsets of immune cells. We investigated associations between each cell type and survival and response to chemotherapy, modelling cellular proportions as quartiles. We found that tumours with little or no immune infiltration were associated with different survival patterns according to oestrogen receptor (ER) status. In ER-negative disease, tumours lacking immune infiltration were associated with the poorest prognosis, whereas in ER-positive disease, they were associated with intermediate prognosis. Of the cell subsets investigated, T regulatory cells and M0 and M2 macrophages emerged as the most strongly associated with poor outcome, regardless of ER status. Among ER-negative tumours, CD8+ T cells (hazard ratio [HR] = 0.89, 95% CI 0.80-0.98; p = 0.02) and activated memory T cells (HR 0.88, 95% CI 0.80-0.97; p = 0.01) were associated with favourable outcome. T follicular help...