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Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment.

ABSTRACT: 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-sequencing 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.

SUBMITTER: Barkley D

PROVIDER: S-EPMC9886402 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment.

Barkley Dalia D Moncada Reuben R Pour Maayan M Liberman Deborah A DA Dryg Ian I Werba Gregor G Wang Wei W Baron Maayan M Rao Anjali A Xia Bo B França Gustavo S GS Weil Alejandro A Delair Deborah F DF Hajdu Cristina C Lund Amanda W AW Osman Iman I Yanai Itai I

Nature genetics 20220805 8

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-sequencing analysis across 15 cancer types and identify a catalog of gene modules whose expression defines recurrent cancer cell states including 'stress', 'interferon response', 'e ...[more]

PMID: 35931863

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Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment.

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Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment.

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