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Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions

Andersson, Alma (author)
KTH Royal Institute of Technology,KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
Larsson, Ludvig (author)
KTH Royal Institute of Technology,KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
Stenbeck, Linnea (author)
KTH Royal Institute of Technology,KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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Salmén, Fredrik (author)
KTH,Science for Life Laboratory, SciLifeLab,Genteknologi,Hubrecht Inst KNAW Royal Netherlands Acad Arts &, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Canc Genom Netherlands, Utrecht, Netherlands.,University Medical Center Utrecht
Ehinger, Anna (author)
Lund University,Lunds universitet,Dept Genet & Pathol, Lab Med Reg Sane, Lund, Sweden.;Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden.,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Regional Laboratories Region Skåne
Wu, Sunny Z. (author)
Garvan Inst Med Res, Kinghorn Canc Ctr, Sydney, NSW, Australia.;St Vincents Clin Sch, Fac Med, Sydney, NSW, Australia.,Garvan Institute of Medical Research
Al-Eryani, Ghamdan (author)
Garvan Inst Med Res, Kinghorn Canc Ctr, Sydney, NSW, Australia.;St Vincents Clin Sch, Fac Med, Sydney, NSW, Australia.,Garvan Institute of Medical Research
Roden, Daniel (author)
Garvan Inst Med Res, Kinghorn Canc Ctr, Sydney, NSW, Australia.;St Vincents Clin Sch, Fac Med, Sydney, NSW, Australia.
Swarbrick, Alex (author)
Garvan Inst Med Res, Kinghorn Canc Ctr, Sydney, NSW, Australia.;St Vincents Clin Sch, Fac Med, Sydney, NSW, Australia.
Borg, Åke (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Frisen, Jonas (author)
Karolinska Institutet
Engblom, Camilla (author)
Karolinska Institutet
Lundeberg, Joakim (author)
KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
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 (creator_code:org_t)
2021-10-14
2021
English.
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra- and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. By integration with single cell data, we spatially map tumor-associated cell types to find tertiary lymphoid-like structures, and a type I interferon response overlapping with regions of T-cell and macrophage subset colocalization. We construct a predictive model to infer presence of tertiary lymphoid-like structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define a high resolution map of cellular interactions in tumors and provide tools generalizing across tissues and diseases. While transcriptomics have enhanced our understanding for cancer, spatial transcriptomics enable the characterisation of cellular interactions. Here, the authors integrate single cell data with spatial information for HER2 + tumours and develop tools for the prediction of interactions between tumour-infiltrating cells.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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