scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory.
scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory.
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DOI：
10.1038/s41467-022-32627-z
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发表时间：
2022-08-23
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
胃癌（GC）的肿瘤微环境（tumor microenvironment， TME）已被证明在肿瘤控制中起重要作用，但胃癌的具体特征尚未得到充分认识。我们从10名胃癌患者的肿瘤旁组织和血液中获得了166533个细胞的图谱。我们的研究结果表明，肿瘤相关基质细胞（TASCs）具有上调的Wnt信号和血管生成活性，并且与生存呈负相关。肿瘤相关巨噬细胞和LAMP3+ dc参与介导T细胞活性，并与tasc形成细胞间相互作用枢纽。克隆型和轨迹分析表明，Tc17 （IL-17+CD8+ T细胞）起源于组织驻留记忆T细胞，随后可分化为耗竭T细胞，提示T细胞耗竭的另一种途径。我们的研究结果表明，IL17+细胞可能通过IL17、IL22和IL26信号通路促进肿瘤进展，突出了靶向IL17+细胞及其相关信号通路作为治疗GC的治疗策略的可能性。胃癌在肿瘤分期和免疫细胞受累程度上各不相同。在这里，作者使用单细胞和TCR测序比较了来自GC患者血液和肿瘤部位的免疫细胞类型中的基因表达，并表明IL17+CD8+ T细胞具有与耗尽细胞相关的表型。
The tumor microenvironment (TME) in gastric cancer (GC) has been shown to be important for tumor control but the specific characteristics for GC are not fully appreciated. We generated an atlas of 166,533 cells from 10 GC patients with matched paratumor tissues and blood. Our results show tumor-associated stromal cells (TASCs) have upregulated activity of Wnt signaling and angiogenesis, and are negatively correlated with survival. Tumor-associated macrophages and LAMP3+ DCs are involved in mediating T cell activity and form intercellular interaction hubs with TASCs. Clonotype and trajectory analysis demonstrates that Tc17 (IL-17+CD8+ T cells) originate from tissue-resident memory T cells and can subsequently differentiate into exhausted T cells, suggesting an alternative pathway for T cell exhaustion. Our results indicate that IL17+ cells may promote tumor progression through IL17, IL22, and IL26 signaling, highlighting the possibility of targeting IL17+ cells and associated signaling pathways as a therapeutic strategy to treat GC. Gastric cancer can vary in tumour stage and immune cell involvement. Here the authors compare gene expression in immune cell types from the blood and the tumour site from GC patients using single cell and TCR sequencing and show that IL17+CD8+ T cells have a phenotype related to that seen with exhausted cells.
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影响因子：
29.4
作者：
Hinoi, T;Lucas, PC;Fearon, ER
通讯作者：
Fearon, ER
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
64.8
作者：
La Manno G;Soldatov R;Zeisel A;Braun E;Hochgerner H;Petukhov V;Lidschreiber K;Kastriti ME;Lönnerberg P;Furlan A;Fan J;Borm LE;Liu Z;van Bruggen D;Guo J;He X;Barker R;Sundström E;Castelo-Branco G;Cramer P;Adameyko I;Linnarsson S;Kharchenko PV
通讯作者：
Kharchenko PV
影响因子：
14.8
作者：
Efremova, Mirjana;Vento-Tormo, Miquel;Vento-Tormo, Roser
通讯作者：
Vento-Tormo, Roser
影响因子：
64.5
作者：
Azizi E;Carr AJ;Plitas G;Cornish AE;Konopacki C;Prabhakaran S;Nainys J;Wu K;Kiseliovas V;Setty M;Choi K;Fromme RM;Dao P;McKenney PT;Wasti RC;Kadaveru K;Mazutis L;Rudensky AY;Pe'er D
通讯作者：
Pe'er D