Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment
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Summary
Transcriptional heterogeneity among malignant cells of a tumor has been studied in individual cancer types and shown to be organized into cancer cell states; however, it remains unclear to what extent these states span tumor types, constituting general features of cancer. Here, we perform a pan-cancer single-cell RNA-Seq analysis across 15 cancer types and identify a catalog of gene modules whose expression defines recurrent cancer cell states including ‘stress’, ‘interferon response’, ‘epithelial-mesenchymal transition’, ‘metal response’, ‘basal’ and ‘ciliated’. Spatial transcriptomic analysis linked the interferon response in cancer cells to T cells and macrophages in the tumor microenvironment. Using mouse models, we further found that induction of the interferon response module varies by tumor location and is diminished upon elimination of lymphocytes. Our work provides a framework for studying how cancer cell states interact with the tumor microenvironment to form organized systems capable of immune evasion, drug resistance, and metastasis.
Transcriptional heterogeneity among malignant cells of a tumor has been studied in individual cancer types and shown to be organized into cancer cell states; however, it remains unclear to what extent these states span tumor types, constituting general features of cancer. Here, we perform a pan-cancer single-cell RNA-Seq analysis across 15 cancer types and identify a catalog of gene modules whose expression defines recurrent cancer cell states including ‘stress’, ‘interferon response’, ‘epithelial-mesenchymal transition’, ‘metal response’, ‘basal’ and ‘ciliated’. Spatial transcriptomic analysis linked the interferon response in cancer cells to T cells and macrophages in the tumor microenvironment. Using mouse models, we further found that induction of the interferon response module varies by tumor location and is diminished upon elimination of lymphocytes. Our work provides a framework for studying how cancer cell states interact with the tumor microenvironment to form organized systems capable of immune evasion, drug resistance, and metastasis.
Overall design
Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment
Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment
Technology
10x Visium
10x Visium
Platform
Illumina NextSeq 500 (Homo sapiens), Illumina NextSeq 500 (Mus musculus), Illumina NextSeq 500 (Homo sapiens; Mus musculus)
Illumina NextSeq 500 (Homo sapiens), Illumina NextSeq 500 (Mus musculus), Illumina NextSeq 500 (Homo sapiens; Mus musculus)
Species
Homo sapiens
Mus musculus
Tissues
Stomach
Stomach
Disease
Breast carcinoma
Breast carcinoma
Citation
Barkley D, Moncada R, Pour M, et al. Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment. Nat Genet. 2022;54(8):1192-1201. doi:10.1038/s41588-022-01141-9
Barkley D, Moncada R, Pour M, et al. Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment. Nat Genet. 2022;54(8):1192-1201. doi:10.1038/s41588-022-01141-9
Submission date: 2022-05-23Update date: 2022-12-11
Sample number: 12Section number: 12
Contributors
Barkley, Dalia; Yanai, Itai
Accessions
GEO Series Accessions:
GSE203612