Description

Genome-wide 3D-transcriptomics reveals localized immune system activity and subtype-heterogeneity in HER2+ breast tumors

Fredrik Salmén¹†, Sanja Vickovic¹†, Linnea Stenbeck¹, Johan Vallon-Christersson², Anna Ehinger^{2, 3}, Jari Häkkinen², Åke Borg², Jonas Frisén⁴, Patrik L Ståhl^{1, 4}*, Joakim Lundeberg¹

¹Science for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden; ²Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden; ³Department of Pathology and Cytology, Blekinge County Hospital, Karlskrona, Sweden; ⁴Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden

†Equal contribution

*Corresponding author

Comprehensive analysis of tumor tissue is crucial for determining specific disease states and establishing suitable treatment plans. Here, we analyze tumor tissue from patients with HER2+ breast cancer to obtain genome-wide three-dimensional expression data. We track regional heterogeneity of ductal cancer in situ with its adjacent regions to reveal a mutually exclusive immune system response in the three-dimensional tumor microenvironment. We also detect and visualize intrinsic molecular subtypes using the AIMS classification system showing that HER2+ breast tumors can contain several distinct subtypes within the same invasive region. The increased granularity provided by detailed spatial transcriptomes throughout a tumor can be used to decipher a number of biological questions, and in turn have a direct impact on the clinical decision-making process.