Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target.
Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target.
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DOI：
10.1038/s41467-022-28372-y
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发表时间：
2022-02-09
影响因子：
16.6
通讯作者：
Yun K
中科院分区：
文献类型：
--
作者：
Abdelfattah N;Kumar P;Wang C;Leu JS;Flynn WF;Gao R;Baskin DS;Pichumani K;Ijare OB;Wood SL;Powell SZ;Haviland DL;Parker Kerrigan BC;Lang FF;Prabhu SS;Huntoon KM;Jiang W;Kim BYS;George J;Yun K
开发更有效的GBM免疫疗法的一个主要限速步骤是我们对胶质瘤中免疫浸润的细胞复杂性和分子异质性的理解不足。在这里，我们报告了在单细胞水平上对201，986个人类胶质瘤、免疫细胞和其他基质细胞的综合分析。在这样做的过程中，我们发现广泛的空间和分子异质性免疫浸润。我们确定了9种不同髓系细胞亚型的分子特征，其中5种是神经胶质瘤患者生存的独立预后指标。此外，我们鉴定了S100A4作为GBM中免疫抑制性T细胞和骨髓细胞的调节剂，并证明在非癌细胞中删除S100a4足以重新编程免疫景观并显着提高生存率。这项研究提供了神经胶质瘤和神经胶质瘤相关免疫细胞的空间，分子和功能异质性的见解，并证明了该数据集用于发现这种免疫原性差的癌症的治疗靶点的实用性。胶质母细胞瘤（GBM）是一种免疫性冷肿瘤，免疫疗法难以治疗。在这里，作者通过单细胞RNA测序鉴定了GBM中免疫抑制和促进骨髓细胞的分子表型，并提出S100A4作为GBM中免疫抑制T细胞和骨髓细胞的调节剂。
A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer. Glioblastoma (GBM) is an immune cold tumour that is refractory to immunotherapy. Here, the authors identify molecular phenotypes of immune-suppressive and -promoting myeloid cells in GBM through single cell RNA sequencing and propose S100A4 as a regulator of immune suppressive T and myeloid cells in GBM.
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影响因子：
11.2
作者：
Harris MA;Yang H;Low BE;Mukherjee J;Guha A;Bronson RT;Shultz LD;Israel MA;Yun K
通讯作者：
Yun K
影响因子：
50.3
作者：
Hara T;Chanoch-Myers R;Mathewson ND;Myskiw C;Atta L;Bussema L;Eichhorn SW;Greenwald AC;Kinker GS;Rodman C;Gonzalez Castro LN;Wakimoto H;Rozenblatt-Rosen O;Zhuang X;Fan J;Hunter T;Verma IM;Wucherpfennig KW;Regev A;Suvà ML;Tirosh I
通讯作者：
Tirosh I
影响因子：
7.3
作者：
Golubinskaya, Veronika;Puttonen, Henri;Savman, Karin
通讯作者：
Savman, Karin
影响因子：
48
作者：
Korsunsky, Ilya;Millard, Nghia;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya
影响因子：
46.9
作者：
Gao R;Bai S;Henderson YC;Lin Y;Schalck A;Yan Y;Kumar T;Hu M;Sei E;Davis A;Wang F;Shaitelman SF;Wang JR;Chen K;Moulder S;Lai SY;Navin NE
通讯作者：
Navin NE