A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer

Summary

Breast cancer is a heterogeneous disease. Tumor cells and associated healthy cells form ecosystems that determine disease progression and response to therapy. To characterize features of breast cancer ecosystems and their associations with clinical data, we analyzed 144 human breast tumor and 50 non-tumor tissue samples using mass cytometry. The expression of 73 proteins in 26 million cells was evaluated using tumor and immune cell-centric antibody panels. Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. High frequencies of PD-L1 ⁺ tumor-associated macrophages and exhausted T cells were found in high-grade ER ⁺ and ER ⁻ tumors. This large-scale, single-cell atlas deepens our understanding of breast tumor ecosystems and suggests that ecosystem-based patient classification will facilitate identification of individuals for precision medicine approaches targeting the tumor and its immunoenvironment.

Graphical Abstract

Highlights

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  Single-cell proteomics reveals tumor and immune cell diversity in tumor ecosystems

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  Breast cancer exhibits tumor cell phenotypic abnormalities and tumor individuality

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  PD-L1 ⁺ TAMs and exhausted T cells are abundant in high-grade ER ⁻ and ER ⁺ tumors

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  Tumor-immune relationships in the tumor ecosystem are patient-stratifying

Abstract

A single-cell atlas of cancer and immune cells reveals distinct tumor ecosystems across breast cancer patients, informing prognosis and, potentially, therapy selection.