A Conceptual Framework for Inducing T Cell-Mediated Immunity Against Glioblastoma.
A Conceptual Framework for Inducing T Cell-Mediated Immunity Against Glioblastoma.
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DOI：
10.1007/s00281-022-00945-5
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发表时间：
2022-09
影响因子：
9
通讯作者：
Wucherpfennig, Kai W.
中科院分区：
文献类型：
--
作者：
Marx, Sascha;Godicelj, Anze;Wucherpfennig, Kai W.
胶质母细胞瘤是一种高度侵袭性的脑肿瘤，治疗选择有限。几个主要的挑战限制了新疗法的发展，包括每个胶质母细胞瘤内肿瘤细胞状态的广泛异质性以及胶质瘤细胞扩散浸润到邻近健康脑组织（包括对侧半球）的能力。T细胞介导的免疫应答可以基于多克隆T细胞群识别不同肿瘤抗原并在整个组织中进行监视的能力来应对这些挑战。在这里，我们将讨论的主要途径，抑制T细胞介导的免疫对胶质母细胞瘤，重点是受体配体系统，胶质瘤细胞和招募骨髓细胞抑制T细胞功能。一个相关的挑战是，胶质母细胞瘤往往是由T细胞浸润不良，这不仅是由抑制性分子途径，而且目前使用的药物，特别是高剂量的皮质类固醇，杀死活化，增殖的T细胞。我们将讨论诱导胶质母细胞瘤导向T细胞反应的创新方法，包括基于新抗原的疫苗和复杂的CAR T细胞方法，可以靶向异质性胶质母细胞瘤细胞群。最后，我们将提出一个概念框架，为未来发展的T细胞为基础的免疫治疗胶质母细胞瘤。
Glioblastoma is a highly aggressive brain tumor with limited treatment options. Several major challenges have limited the development of novel therapeutics, including the extensive heterogeneity of tumor cell states within each glioblastoma and the ability of glioma cells to diffusely infiltrate into neighboring healthy brain tissue, including the contralateral hemisphere. A T cell-mediated immune response could deal with these challenges based on the ability of polyclonal T cell populations to recognize diverse tumor antigens and perform surveillance throughout tissues. Here we will discuss the major pathways that inhibit T cell-mediated immunity against glioblastoma, with an emphasis on receptor–ligand systems by which glioma cells and recruited myeloid cells inhibit T cell function. A related challenge is that glioblastomas tend to be poorly infiltrated by T cells, which is not only caused by inhibitory molecular pathways but also currently utilized drugs, in particular high-dose corticosteroids that kill activated, proliferating T cells. We will discuss innovative approaches to induce glioblastoma-directed T cell responses, including neoantigen-based vaccines and sophisticated CAR T cell approaches that can target heterogeneous glioblastoma cell populations. Finally, we will propose a conceptual framework for the future development of T cell-based immunotherapies for glioblastoma.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
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作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
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Urba WJ
影响因子：
16.6
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Ashley DM
影响因子：
64.5
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通讯作者：
Pollard SM
影响因子：
8
作者：
Guerrero PA;Tchaicha JH;Chen Z;Morales JE;McCarty N;Wang Q;Sulman EP;Fuller G;Lang FF;Rao G;McCarty JH
通讯作者：
McCarty JH
DOI：
10.1158/1078-0432.ccr-15-1535
发表时间：
2017-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kim JE;Patel MA;Mangraviti A;Kim ES;Theodros D;Velarde E;Liu A;Sankey EW;Tam A;Xu H;Mathios D;Jackson CM;Harris-Bookman S;Garzon-Muvdi T;Sheu M;Martin AM;Tyler BM;Tran PT;Ye X;Olivi A;Taube JM;Burger PC;Drake CG;Brem H;Pardoll DM;Lim M
通讯作者：
Lim M