小柯机器人

美国弗雷德·哈钦森癌症研究中心Susan Bullman等研究人员合作揭示瘤内微生物群对癌症的空间和细胞异质性的影响。相关论文于2022年11月16日在线发表于国际学术期刊《自然》。

通过将原位空间分析技术和单细胞RNA测序应用于口腔鳞状细胞癌和结直肠癌，研究人员揭示了空间、细胞和分子的宿主-微生物相互作用。研究人员调整了10倍Visium空间转录组学，以确定患者组织内瘤内微生物群落的身份和原位位置。使用GeoMx数字空间剖析，研究人员表明，细菌群落填充在血管较少、高度免疫抑制和与恶性细胞相关的微生态环境中，与细菌阴性的肿瘤区域相比，Ki-67水平较低。研究人员开发了一种单细胞RNA测序方法，被称为INVADEseq（入侵-粘附-定向表达测序），并通过将其应用于患者肿瘤，确定了细胞相关的细菌和与之相互作用的宿主细胞，并发现了参与炎症、转移、细胞休眠和DNA修复的转录途径的变化。

通过功能研究，研究人员表明，被细菌感染的癌细胞作为单细胞入侵其周围环境，并招募骨髓细胞到细菌区域。总之，这些数据显示，肿瘤内微生物群的分布不是随机的；相反，它是高度组织化的，具有促进癌症发展的免疫和上皮细胞功能的微循环。

据悉，肿瘤相关的微生物群是各种人类癌症类型的肿瘤微环境的内在组成部分。迄今为止，肿瘤内宿主微生物群的研究主要依赖于大量的组织分析，这掩盖了肿瘤内微生物群的空间分布和局部效应。

附：英文原文

Title: Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer

Author: Nio, Jorge Luis Galeano, Wu, Hanrui, LaCourse, Kaitlyn D., Kempchinsky, Andrew G., Baryiames, Alexander, Barber, Brittany, Futran, Neal, Houlton, Jeffrey, Sather, Cassie, Sicinska, Ewa, Taylor, Alison, Minot, Samuel S., Johnston, Christopher D., Bullman, Susan

Issue&Volume: 2022-11-16

Abstract: The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types1,2. Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis1,2,3, which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies4 and single-cell RNA sequencing5 to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host–microbe interactions. We adapted 10x Visium spatial transcriptomics to determine the identity and in situ location of intratumoral microbial communities within patient tissues. Using GeoMx digital spatial profiling6, we show that bacterial communities populate microniches that are less vascularized, highly immunosuppressive and associated with malignant cells with lower levels of Ki-67 as compared to bacteria-negative tumour regions. We developed a single-cell RNA-sequencing method that we name INVADEseq (invasion–adhesion-directed expression sequencing) and, by applying this to patient tumours, identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair. Through functional studies, we show that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells to bacterial regions. Collectively, our data reveal that the distribution of the microbiota within a tumour is not random; instead, it is highly organized in microniches with immune and epithelial cell functions that promote cancer progression.

DOI: 10.1038/s41586-022-05435-0

Source: https://www.nature.com/articles/s41586-022-05435-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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