Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties.
Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties.
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儿童脑肿瘤中的肿瘤内 T 细胞表现出克隆扩张和效应特性。
DOI：
10.1038/s43018-023-00706-9
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发表时间：
2024
期刊：
影响因子：
22.7
通讯作者：
中科院分区：
文献类型：
--
作者：
Upadhye,Aditi;MezaLanderos,KevinE;Ramírez-Suástegui,Ciro;Schmiedel,BenjaminJ;Woo,Edwin;Chee,SerenaJ;Malicki,Denise;Coufal,NicoleG;Gonda,David;Levy,MichaelL;Greenbaum,JasonA;Seumois,Grégory;Crawford,John;Roberts,WilliamD;
Brain tumors in children are a devastating disease in a high proportion of patients. Owing to inconsistent results in clinical trials in unstratified patients, the role of immunotherapy remains unclear. We performed an in-depth survey of the single-cell transcriptomes and clonal relationship of intra-tumoral T cells from children with brain tumors. Our results demonstrate that a large fraction of T cells in the tumor tissue are clonally expanded with the potential to recognize tumor antigens. Such clonally expanded T cells display enrichment of transcripts linked to effector function, tissue residency, immune checkpoints and signatures of neoantigen-specific T cells and immunotherapy response. We identify neoantigens in pediatric brain tumors and show that neoantigen-specific T cell gene signatures are linked to better survival outcomes. Notably, among the patients in our cohort, we observe substantial heterogeneity in the degree of clonal expansion and magnitude of T cell response. Our findings suggest that characterization of intra-tumoral T cell responses may enable selection of patients for immunotherapy, an approach that requires prospective validation in clinical trials.
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影响因子：
64.5
作者：
Tim Stuart;Andrew Butler;Paul J. Hoffman;Christoph Hafemeister;Efthymia Papalexi;William M. Mauck;
通讯作者：
Tim Stuart;Andrew Butler;Paul J. Hoffman;Christoph Hafemeister;Efthymia Papalexi;William M. Mauck;
影响因子：
64.5
作者：
Meckiff BJ;Ramírez-Suástegui C;Fajardo V;Chee SJ;Kusnadi A;Simon H;Eschweiler S;Grifoni A;Pelosi E;Weiskopf D;Sette A;Ay F;Seumois G;Ottensmeier CH;Vijayanand P
通讯作者：
Vijayanand P
影响因子：
17.1
作者：
通讯作者：
--
影响因子：
7.3
作者：
Behr, Felix M.;Kragten, Natasja A. M.;van Gisbergen, Klaas P. J. M.
通讯作者：
van Gisbergen, Klaas P. J. M.
影响因子：
22.7
作者：
Liu, Baolin;Hu, Xueda;Zhang, Zemin
通讯作者：
Zhang, Zemin