Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis.
Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis.
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DOI：
10.1186/s12964-023-01322-x
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发表时间：
2023-11-13
影响因子：
8.4
通讯作者：
Zhang, Xiaoju
中科院分区：
文献类型：
--
作者：
Wang, Ziqi;Yang, Li;Wang, Wenqiang;Zhou, Huanhuan;Chen, Juan;Ma, Zeheng;Wang, Xiaoyan;Zhang, Quncheng;Liu, Haiyang;Zhou, Chao;Guo, Zhiping;Zhang, Xiaoju
癌前病变向早期肺腺癌（LUAD）的恶性进展及其惰性本质的机制仍然难以捉摸。对5例正常肺组织、3例癌前病变和4例早期LUAD患者的肺磨玻璃样结节（GGN）进行单细胞RNA测序（scRNA）和同步T细胞受体（TCR）测序。通过这种综合分析，我们已经划定了五个关键模块，驱动恶性进展的早期LUAD的疾病阶段依赖性的方式。这些模块与细胞增殖和代谢、免疫应答、线粒体、纤毛和细胞粘附有关。我们还发现，早期LUAD表现为GGN的肿瘤微环境（TME）的特征是具有三种可能来源的调节性T细胞（Tlymphocyte，Tlymphocyte）积聚，以及CD 8 + T细胞的功能丧失状态（克隆扩增和细胞毒性降低）。CD 8 + T细胞不是衰竭，而是向记忆表型转变，这与晚期LUAD显著不同。此外，我们已经确定了单核细胞衍生的巨噬细胞，经历了脂质表型转变，并可能有助于抑制性TME。还表征了基质细胞、骨髓细胞（包括脂质相关巨噬细胞和LAMP 3 + DC）和淋巴细胞之间的强烈相互作用。我们的工作为LUAD恶性进展表现为GGN的分子和细胞机制提供了新的见解，并为GGN的新型免疫治疗铺平了道路。视频摘要在线版本包含补充材料，可通过10. 1186/s12964-023-01322-x获取。
Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract The online version contains supplementary material available at 10.1186/s12964-023-01322-x.
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影响因子：
5.4
作者：
Donahue, Daniel;Porrot, FranOoise;Schwartz, Olivier
通讯作者：
Schwartz, Olivier
影响因子：
8.8
作者：
Aras S;Zaidi MR
通讯作者：
Zaidi MR
影响因子：
4.4
作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
通讯作者：
Haller, David A.
DOI：
10.1164/rccm.201911-2199oc
发表时间：
2020-12-15
影响因子：
24.7
作者：
Deprez, Marie;Zaragosi, Laure-Emmanuelle;Barbry, Pascal
通讯作者：
Barbry, Pascal
影响因子：
28.2
作者：
Humpton, Timothy J.;Alagesan, Brinda;Tuveson, David A.
通讯作者：
Tuveson, David A.