单细胞转录组分析发现了一种新型肿瘤相关巨噬细胞亚型,可预测胰腺导管腺癌的较佳预后。

IF 4.6 2区 生物学 Q2 CELL BIOLOGY Frontiers in Cell and Developmental Biology Pub Date : 2024-10-23 eCollection Date: 2024-01-01 DOI:10.3389/fcell.2024.1466767
Xiaonan Wang, Dongyi Li, Bo Zhu, Zichun Hua
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引用次数: 0

摘要

背景:胰腺导管腺癌(PDAC)以免疫抑制性肿瘤微环境(TME)为特征,以预后不良而闻名。肿瘤相关巨噬细胞(TAMs)在 PDAC TME 中发挥着关键作用。深入了解 TAMs 有助于开发新的免疫疗法策略:方法:收集大量 PDAC 的单细胞 RNA 测序数据和批量 RNA 测序数据,进行系统的生物信息学分析。以单细胞分辨率描述TAMs亚型及其对预后的影响。使用差异基因分析和细胞间通讯来描述对预后的影响,并通过 TCGA 数据集进行验证:通过分析PDAC的scRNA-seq数据和大量RNA数据,我们利用SLC12A5和ENPP2这两个对预后有利的基因鉴定出了良性M2样TAMs(bM2-like TAMs),它们与C1QC + TAMs、CXCL9+ TAMs和CD169+ TAMs有相似之处。研究发现,bM2 样 TAMs 可通过 ALCAM/CD6 相互作用促进 T 细胞的活化和增殖。同时,bM2-like TAMs通过改变αSMA+/αSMA-细胞的比例负责基质的建模。相比之下,其余的M2样TAMs被定义为恶性M2样TAMs(mM2样TAMs),与SPP1+ TAMs部分重叠:我们的研究利用两个对预后有利的基因将PDAC的M2样TAMs分为抗肿瘤的bM2样TAMs和促肿瘤的mM2样TAMs。bM2样TAMs通过ALCAM/CD6激活T细胞,并通过分泌TGFβ生成预后良好的αSMA+肌成纤维细胞,这为TAMs的异质性、预后预测和PDAC的免疫治疗带来了启示。
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Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma.

Background: Characterized by an immune-suppressive tumor microenvironment (TME), pancreatic ductal adenocarcinoma (PDAC) is well-known for its poor prognosis. Tumor associated macrophages (TAMs) play a critical role in PDAC TME. An in-depth understanding of TAMs is helpful to develop new strategies for immunotherapy.

Methods: A large number of single-cell RNA sequencing data and bulk RNA sequencing data of PDAC were collected for systematic bioinformatics analysis. Characterize subtypes of TAMs at single-cell resolution and its effect on prognosis. Differential gene analysis and cell-cell communication were used to describe the effect on prognosis and validated by the TCGA dataset.

Results: We used two prognosis-favorable genes, SLC12A5 and ENPP2, to identify a benign M2-like TAMs (bM2-like TAMs), which shared similarities with C1QC + TAMs, CXCL9+ TAMs and CD169+ TAMs, by analyzing scRNA-seq data and bulk RNA data of PDAC. The bM2-like TAMs were revealed to promote T cell activation and proliferation through ALCAM/CD6 interaction. Meanwhile, the bM2-like TAMs were responsible for stroma modeling by altering αSMA+/αSMA-cell ratio. On the contrast, the rest of the M2-like TAMs were defined as malignant M2-like TAMs (mM2-like TAMs), partly overlapping with SPP1+ TAMs. mM2-like TAMs were revealed to promote tumor progression by secretion of MIF and SPP1.

Conclusion: Our study used two prognosis-favorable genes to divide M2-like TAMs of PDAC into anti-tumor bM2-like TAMs and pro-tumor mM2-like TAMs. The bM2-like TAMs activate T cells through ALCAM/CD6 and generate prognosis-favorable αSMA+ myofibroblasts through secreting TGFβ, which brings insight into heterogeneity of TAMs, prognosis prediction and immunotherapy of PDAC.

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来源期刊
Frontiers in Cell and Developmental Biology
Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
9.70
自引率
3.60%
发文量
2531
审稿时长
12 weeks
期刊介绍: Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.
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