Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity.
Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity.
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DOI：
10.1084/jem.20170229
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发表时间：
2017-08-07
期刊：
影响因子：
--
通讯作者：
Amigorena S
中科院分区：
文献类型：
--
作者：
Alloatti A;Rookhuizen DC;Joannas L;Carpier JM;Iborra S;Magalhaes JG;Yatim N;Kozik P;Sancho D;Albert ML;Amigorena S
Alloatti等人表明，Sec 22 b依赖性抗原交叉呈递对于产生有效的抗肿瘤CD 8 + T细胞应答至关重要。树突状细胞中Sec 22 b的条件性缺失降低了对死细胞的免疫应答，并促进了对抗PD-1免疫疗法的抵抗。CD 8 + T细胞介导抗原特异性免疫应答，可诱导实体瘤的排斥反应。在这个过程中，树突状细胞（DC）被认为会摄取肿瘤抗原，这些抗原被加工成肽并加载到MHC-I分子上，这一过程称为“交叉呈递”。由于缺乏实验工具来操纵这一过程，交叉呈递对抗肿瘤免疫应答的实际贡献和体内涉及的细胞内途径都没有明确建立。为了开发这样的工具，我们产生了在sec 22 b基因中具有条件性DC特异性突变的小鼠，sec 22 b基因是交叉呈递所需的内质网-吞噬体交通的关键调节因子。来自这些小鼠的DC显示出离体交叉呈递受损和体内CD 8 + T细胞应答的交叉引发缺陷。这些小鼠也缺乏抗肿瘤免疫应答，并且对抗PD-1治疗具有抗性。我们的结论是，在DC中的Sec 22 b依赖性交叉呈递是启动CD 8 + T细胞对死细胞的应答并在小鼠中抗PD-1治疗期间诱导有效的抗肿瘤免疫应答所必需的。
Alloatti et al. show that Sec22b-dependent antigen cross-presentation is critical to developing effective antitumor CD8+ T cell responses. Conditional deletion of Sec22b in dendritic cells decreases immune response against dead cells and promotes resistance to immunotherapy with anti–PD-1. CD8+ T cells mediate antigen-specific immune responses that can induce rejection of solid tumors. In this process, dendritic cells (DCs) are thought to take up tumor antigens, which are processed into peptides and loaded onto MHC-I molecules, a process called “cross-presentation.” Neither the actual contribution of cross-presentation to antitumor immune responses nor the intracellular pathways involved in vivo are clearly established because of the lack of experimental tools to manipulate this process. To develop such tools, we generated mice bearing a conditional DC-specific mutation in the sec22b gene, a critical regulator of endoplasmic reticulum–phagosome traffic required for cross-presentation. DCs from these mice show impaired cross-presentation ex vivo and defective cross-priming of CD8+ T cell responses in vivo. These mice are also defective for antitumor immune responses and are resistant to treatment with anti–PD-1. We conclude that Sec22b-dependent cross-presentation in DCs is required to initiate CD8+ T cell responses to dead cells and to induce effective antitumor immune responses during anti–PD-1 treatment in mice.
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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：
--
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
通讯作者：
Urba WJ
DOI：
10.1084/jem.20061890
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Boissonnas A;Fetler L;Zeelenberg IS;Hugues S;Amigorena S
通讯作者：
Amigorena S
影响因子：
64.5
作者：
Nair-Gupta P;Baccarini A;Tung N;Seyffer F;Florey O;Huang Y;Banerjee M;Overholtzer M;Roche PA;Tampé R;Brown BD;Amsen D;Whiteheart SW;Blander JM
通讯作者：
Blander JM
影响因子：
64.5
作者：
Eickhoff S;Brewitz A;Gerner MY;Klauschen F;Komander K;Hemmi H;Garbi N;Kaisho T;Germain RN;Kastenmüller W
通讯作者：
Kastenmüller W
影响因子：
28.2
作者：
Sánchez-Paulete AR;Cueto FJ;Martínez-López M;Labiano S;Morales-Kastresana A;Rodríguez-Ruiz ME;Jure-Kunkel M;Azpilikueta A;Aznar MA;Quetglas JI;Sancho D;Melero I
通讯作者：
Melero I