scholarly journals Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships

2020 ◽  
Author(s):  
Alma Andersson ◽  
Ludvig Larsson ◽  
Linnea Stenbeck ◽  
Fredrik Salmén ◽  
Anna Ehinger ◽  
...  

ABSTRACTIn 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. We integrate and spatially map tumor-associated types from single cell data to find: segregated epithelial cells, interactions between B and T-cells and myeloid cells, co-localization of macrophage and T-cell subsets. A model is constructed to infer presence of tertiary lymphoid structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define novel interactions between tumor-infiltrating cells in breast cancer and provide tools generalizing across tissues and diseases.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alma Andersson ◽  
Ludvig Larsson ◽  
Linnea Stenbeck ◽  
Fredrik Salmén ◽  
Anna Ehinger ◽  
...  

AbstractIn 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.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luuk van Hooren ◽  
Alessandra Vaccaro ◽  
Mohanraj Ramachandran ◽  
Konstantinos Vazaios ◽  
Sylwia Libard ◽  
...  

AbstractGliomas are brain tumors characterized by an immunosuppressive microenvironment. Immunostimulatory agonistic CD40 antibodies (αCD40) are in clinical development for solid tumors, but are yet to be evaluated for glioma. Here, we demonstrate that systemic delivery of αCD40 in preclinical glioma models induces the formation of tertiary lymphoid structures (TLS) in proximity of meningeal tissue. In treatment-naïve glioma patients, the presence of TLS correlates with increased T cell infiltration. However, systemic delivery of αCD40 induces hypofunctional T cells and impairs the response to immune checkpoint inhibitors in pre-clinical glioma models. This is associated with a systemic induction of suppressive CD11b+ B cells post-αCD40 treatment, which accumulate in the tumor microenvironment. Our work unveils the pleiotropic effects of αCD40 therapy in glioma and reveals that immunotherapies can modulate TLS formation in the brain, opening up for future opportunities to regulate the immune response.


2020 ◽  
Vol 231 (4) ◽  
pp. S264
Author(s):  
Kevin Tyler Lynch ◽  
Max Meneveau ◽  
Samuel Young ◽  
Nolan Wages ◽  
Craig Lee Slingluff ◽  
...  

2019 ◽  
Vol 20 (3) ◽  
Author(s):  
Brunella Restucci ◽  
Ludovico Dipineto ◽  
Manuela Martano ◽  
Anna Balestrieri ◽  
Davide Ciccarelli ◽  
...  

2018 ◽  
Vol 4 (1) ◽  
pp. 137-137
Author(s):  
Madhuri Koti ◽  
Amanda Shuo Xu ◽  
Kevin Yi Mi Ren ◽  
Kash Visram ◽  
Runhan Ren ◽  
...  

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