小柯机器人

美国纽约大学Itai Yanai小组发现，癌细胞状态在不同的肿瘤类型中反复出现并与肿瘤微环境形成特定的相互作用。这一研究成果发表在2022年8月5日出版的国际学术期刊《自然—遗传学》上。

研究人员对15种癌症类型进行了泛癌症单细胞RNA测序分析，并确定了一个基因模块目录，其表达定义了反复出现的癌症细胞状态，包括"压力"、"干扰素响应"、"上皮-间质转化"、"金属响应"、"基质"和"纤毛"。空间转录组分析将癌细胞的干扰素响应与肿瘤微环境中的T细胞和巨噬细胞联系起来。

利用小鼠模型，研究人员进一步发现，干扰素响应模块的诱导因肿瘤位置而异，并且在消除淋巴细胞后会减弱。这项工作提供了一个框架，可用于研究癌细胞状态如何与肿瘤微环境相互作用，形成有组织的系统，进而能够进行免疫规避、耐药和转移。

据了解，肿瘤恶性细胞之间的转录异质性已在个别癌症类型中得到研究，并被证明组织成了癌细胞状态；然而，仍然不清楚这些状态在何种程度上跨越了肿瘤类型，构成了癌症的通用特征。

附：英文原文

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

Author: Barkley, Dalia, Moncada, Reuben, Pour, Maayan, Liberman, Deborah A., Dryg, Ian, Werba, Gregor, Wang, Wei, Baron, Maayan, Rao, Anjali, Xia, Bo, Frana, Gustavo S., Weil, Alejandro, Delair, Deborah F., Hajdu, Cristina, Lund, Amanda W., Osman, Iman, Yanai, Itai

Issue&Volume: 2022-08-05

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.

DOI: 10.1038/s41588-022-01141-9

Source: https://www.nature.com/articles/s41588-022-01141-9

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex