Macrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality.
Macrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality.
复制标题
DOI：
10.1016/j.celrep.2021.108917
复制
发表时间：
2021-03-30
期刊：
影响因子：
8.8
通讯作者：
Haldar, Malay
中科院分区：
文献类型：
--
作者：
Dang, Mai T.;Gonzalez, Michael, V;Gaonkar, Krutika S.;Rathi, Komal S.;Young, Patricia;Arif, Sherjeel;Zhai, Li;Alam, Zahidul;Devalaraja, Samir;To, Tsun Ki Jerrick;Folkert, Ian W.;Raman, Pichai;Rokita, Jo Lynne;Martinez, Daniel;Taroni, Jaclyn N.;Shapiro, Joshua A.;Greene, Casey S.;Savonen, Candace;Mafra, Fernanda;Hakonarson, Hakon;Curran, Tom;Haldar, Malay
肿瘤相关巨噬细胞（tam）在肿瘤免疫中发挥重要作用，由具有不同表型、功能和本体的亚群组成。人类髓母细胞瘤是最常见的儿童恶性脑癌，其转录组学分析显示，具有激活sonic hedgehog信号（sh -MB）的髓母细胞瘤（MBs）比其他MB亚型具有更多的tam。因此，我们通过对稳态和两种不同治疗方式（分子靶向抑制剂和辐射）下的本地小鼠SHH-MB进行单细胞RNA测序来检测mb相关的tam。我们的分析揭示了显著的TAM异质性，鉴定了本体论上不同的TAM亚群标记物，并显示了脑微环境对肿瘤浸润单核细胞分化的影响。TAM组成在治疗过程中发生显著变化，在分子靶向治疗和放射治疗之间存在显著差异。我们发现了放射治疗中出现的免疫抑制单核细胞来源的TAM亚群，并证明了其在MB中调节T细胞和中性粒细胞浸润的作用。Dang等人发现髓母细胞瘤（SHH-MB）的超音hedgehog亚群含有来自小胶质细胞和循环单核细胞的巨噬细胞。放射治疗，而不是靶向SHH通路的治疗，导致免疫抑制性单核细胞源性巨噬细胞的募集，从而减少肿瘤微环境中的T细胞和中性粒细胞。
Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation. Our analyses reveal significant TAM heterogeneity, identify markers of ontologically distinct TAM subsets, and show the impact of brain microenvironment on the differentiation of tumor-infiltrating monocytes. TAM composition undergoes dramatic changes with treatment and differs significantly between molecular-targeted and radiation therapy. We identify an immunosuppressive monocyte-derived TAM subset that emerges with radiation therapy and demonstrate its role in regulating T cell and neutrophil infiltration in MB. Dang et al. show that the sonic hedgehog subgroup of medulloblastoma (SHH-MB) contains macrophages derived from microglia and circulating monocytes. Radiation therapy, but not treatment targeting the SHH pathway, led to recruitment of immunosuppressive monocyte-derived macrophages that reduced T cells and neutrophils in the tumor microenvironment.
登录
查看更多内容
影响因子：
64.8
作者：
Hovestadt, Volker;Smith, Kyle S.;Northcott, Paul A.
通讯作者：
Northcott, Paul A.
高维分析描述了成功的免疫检查癌症治疗过程中髓样和淋巴室的重塑。
影响因子：
64.5
作者：
Gubin MM;Esaulova E;Ward JP;Malkova ON;Runci D;Wong P;Noguchi T;Arthur CD;Meng W;Alspach E;Medrano RFV;Fronick C;Fehlings M;Newell EW;Fulton RS;Sheehan KCF;Oh ST;Schreiber RD;Artyomov MN
通讯作者：
Artyomov MN
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：
5.3
作者：
Ginhoux F;Lim S;Hoeffel G;Low D;Huber T
通讯作者：
Huber T
影响因子：
16.2
作者：
Bennett FC;Bennett ML;Yaqoob F;Mulinyawe SB;Grant GA;Hayden Gephart M;Plowey ED;Barres BA
通讯作者：
Barres BA