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

人类乳腺癌肿瘤和免疫生态系统的单细胞图谱

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作者:Johanna Wagner ,Maria Anna Rapsomaniki ,Stéphane Chevrier ,Tobias Anzeneder ,Claus Langwieder ,August Dykgers ,Martin Rees ,Annette Ramaswamy ,Simone Muenst ,Savas Deniz Soysal ,Andrea Jacobs ,Jonas Windhager ,Karina Silina ,Maries van den Broek ,Konstantin Johannes Dedes ,Maria Rodríguez Martínez ,Walter Paul Weber ,Bernd Bodenmiller

Abstract

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.

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