CNS tumor stroma transcriptomics identify perivascular fibroblasts as predictors of immunotherapy resistance in glioblastoma patients.
CNS tumor stroma transcriptomics identify perivascular fibroblasts as predictors of immunotherapy resistance in glioblastoma patients.
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DOI：
10.1038/s41525-023-00381-w
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发表时间：
2023-10-26
影响因子：
5.3
通讯作者：
Datta, Meenal
中科院分区：
文献类型：
--
作者：
Zarodniuk, Maksym;Steele, Alexander;Lu, Xin;Li, Jun;Datta, Meenal
细胞外基质（ECM）的过度沉积是实体瘤的标志;然而，对于哪些细胞和分子组分有助于中枢神经系统（CNS）肿瘤中ECM基质的形成仍然知之甚少。在这里，我们进行了回顾性基因表达数据集的泛中枢神经系统分析，以表征成人和儿童中枢神经系统疾病中ECM重塑特征的肿瘤间和肿瘤内异质性。我们发现，中枢神经系统病变-胶质母细胞瘤特别是-可以分为两个基于ECM的亚型（ECMhi和ECMlo），这是由血管周围的基质细胞类似于癌症相关的成纤维细胞（CAF）的存在的影响。配体-受体网络分析预测血管周围成纤维细胞激活负责肿瘤相关巨噬细胞募集和促进癌症干性的信号通路。我们的分析表明，血管周围成纤维细胞与胶质母细胞瘤中对免疫检查点阻断的不利反应以及CNS肿瘤亚组中患者生存率低相关。我们提供了新的基质驱动机制的免疫逃避和免疫治疗耐药性的中枢神经系统肿瘤，如胶质母细胞瘤的见解，并讨论如何靶向这些血管周围成纤维细胞可能证明是一种有效的方法，以改善治疗反应和患者的生存在各种中枢神经系统肿瘤。
Excessive deposition of extracellular matrix (ECM) is a hallmark of solid tumors; however, it remains poorly understood which cellular and molecular components contribute to the formation of ECM stroma in central nervous system (CNS) tumors. Here, we undertake a pan-CNS analysis of retrospective gene expression datasets to characterize inter- and intra-tumoral heterogeneity of ECM remodeling signatures in both adult and pediatric CNS disease. We find that CNS lesions – glioblastoma in particular – can be divided into two ECM-based subtypes (ECMhi and ECMlo) that are influenced by the presence of perivascular stromal cells resembling cancer-associated fibroblasts (CAFs). Ligand-receptor network analysis predicts that perivascular fibroblasts activate signaling pathways responsible for recruitment of tumor-associated macrophages and promotion of cancer stemness. Our analysis reveals that perivascular fibroblasts are correlated with unfavorable response to immune checkpoint blockade in glioblastoma and poor patient survival across a subset of CNS tumors. We provide insights into new stroma-driven mechanisms underlying immune evasion and immunotherapy resistance in CNS tumors like glioblastoma, and discuss how targeting these perivascular fibroblasts may prove an effective approach to improving treatment response and patient survival in a variety of CNS tumors.
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影响因子：
64.5
作者：
Dias DO;Kim H;Holl D;Werne Solnestam B;Lundeberg J;Carlén M;Göritz C;Frisén J
通讯作者：
Frisén J
DOI：
10.1073/pnas.2219199120
发表时间：
2023-02-07
影响因子：
11.1
作者：
Datta, Meenal;Chatterjee, Sampurna;Perez, Elizabeth M.;Gritsch, Simon;Roberge, Sylvie;Duquette, Mark;Chen, Ivy X.;Naxerova, Kamila;Kumar, Ashwin S.;Ghosh, Mitraji;Emblem, Kyrre E.;Ng, Mei R.;Ho, Willia W.;Kumar, Pragya;Krsihnan, Shanmugaraja;Dong, Xinyu;Speranza, Maria C.;Neagu, Martha R.;Iorgulescu, Bryan;Huang, Raymond Y.;Youssef, Gilbert;Reardon, David A.;Sharpe, Arlene H.;Freeman, Gordon J.;Suva, Mario L.;Xu, Lei;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
16.6
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
通讯作者：
Yun K
影响因子：
8
作者：
Garcia-Palmero, I.;Torres, S.;Casal, J. I.
通讯作者：
Casal, J. I.
影响因子：
50.3
作者：
Hoogstrate, Youri;Draaisma, Kaspar;French, Pim J.
通讯作者：
French, Pim J.