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Given the contribution of the tumor microenvironment (TME) to cancer development and response to treatment, we analyzed here how chemotherapy alters the TME in SCLC using single\u2010cell RNA sequencing. The comparison between neuroendocrine cells and other epithelial cells in five chemotherapy\u2010naive patients identified upregulation of Notch\u2010inhibiting genes, such as <jats:italic>DLL3<\/jats:italic> and <jats:italic>HES6<\/jats:italic>. Analysis of genes differentially expressed between five patients receiving chemotherapy and five treatment\u2010naive patients in cells in the TME showed that chemotherapy promoted antigen presentation and senescence in neuroendocrine cells, upregulated <jats:italic>ID1<\/jats:italic> to enhance angiogenic activities of stalk\u2010like endothelial cells and strengthened vascular endothelial growth factor signaling in lymphatic endothelial cells. Chemotherapy also promoted the remodeling of extracellular matrix by fibroblasts and upregulated interferon\u2010mediated antitumor immune responses by B and T cells. Our single\u2010cell transcriptome analysis provides insights into how chemotherapy affects the TME in SCLC, which may guide efforts to make therapy more effective.<\/jats:p>","DOI":"10.1002\/ijc.34629","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T07:54:57Z","timestamp":1687161297000},"page":"1273-1286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Single\u2010cell transcriptome analysis reveals cellular and molecular alterations in small cell lung cancer tumors following chemotherapy"],"prefix":"10.1002","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4609-0411","authenticated-orcid":false,"given":"Cheng","family":"Cheng","sequence":"first","affiliation":[{"name":"Institute of Respiratory Health, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu 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