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.
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DOI:
10.1038/s41588-022-01141-9
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发表时间:
2022-08
期刊:
影响因子:
30.8
通讯作者:
Yanai, Itai
Yanai, Itai
中科院分区:
生物学1区
文献类型:
--
作者:
Barkley, Dalia;Moncada, Reuben;Pour, Maayan;Liberman, Deborah A.;Dryg, Ian;Werba, Gregor;Wang, Wei;Baron, Maayan;Rao, Anjali;Xia, Bo;Franca, Gustavo S.;Weil, Alejandro;Delair, Deborah F.;Hajdu, Cristina;Lund, Amanda W.;Osman, Iman;Yanai, Itai

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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.
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