Using scRNAseq, Lodi et al. created a pan-cancer single-cell atlas from 160 patients across 9 cancer types, and identified 70 shared cell subtypes. Two distinct hubs with subtype abundances that positively correlated with each other were identified. The first hub consisted of differentiated B cells resembling tertiary lymphoid structures, and the second hub consisted of inflammatory macrophages, PD-L1+ immune-regulatory cells, lymphatic ECs, and PD-1+ T cells. Spatial transcriptomic confirmed that cell subtypes in each hub formed a spatially defined TME, and tumors enriched for both hubs correlated with T cell reactivity and responses to ICB.
Contributed by Shishir Pant
ABSTRACT: Pan-cancer single-cell atlases explore the heterogeneity of cell types residing within the tumor microenvironment (TME). So far, atlases focused on individual cell types, failing to capture the full complexity of the TME. Here, we present a single-cell atlas that simultaneously considers heterogeneity in 5 cell types, collected from 230 treatment-naive samples across 9 cancer types. We identify 70 pan-cancer single-cell subtypes, investigate their patterns of co-occurrence and show an enrichment of specific subtypes in certain TMEs, e.g., immune-reactive versus immune-suppressive TME. We observe two TME hubs of strongly co-occurring subtypes: one hub resembling tertiary lymphoid structures (TLSs), another consisting of immune-reactive PD1+/PD-L1+ immune-regulatory T cells and B cells, dendritic cells and inflammatory macrophages. Subtypes belonging to each hub are spatially co-localized, while their abundance associates with early and long-term checkpoint immunotherapy response. We publicly share our atlas using a Shiny app, allowing others to explore TME heterogeneity in different biological contexts.
Author Info: 1- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
2- VIB Center for Cancer Biology, Leuven, Belgium
3- Zhejiang Key Laboratory of P
Author Info: 1- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
2- VIB Center for Cancer Biology, Leuven, Belgium
3- Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
4- Laboratory for Molecular Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium
5- Digestive Oncology, Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium
6- Department of Pneumology, Division of Respiratory Oncology, University Hospitals Leuven, Leuven, Belgium
7- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
8- Bioinformatics Expertise Center, VIB Center for Cancer Biology, Leuven, Belgium
9- Department of Obstetrics and Gynaecology, Division of Gynaecological Oncology, University Hospitals Leuven, Leuven, Belgium
10- Laboratory of Gynaecologic Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
11- Department of General Medical Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
12- Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium
13- Department of Surgical Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
14- Department of Radiology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
15- Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
16- Leuven Institute for Single-cell Omics (LISCO), KU Leuven, Leuven, Belgium
17- Laboratory of Tumor Microenvironment and Therapeutic Resistance, Department of Oncology, KU Leuven, Leuven, Belgium
18- Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, China
19- Lead contact
