Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer.
Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer.
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DOI：
10.3389/fimmu.2018.02030
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发表时间：
2018
影响因子：
7.3
通讯作者：
Ngwa W
中科院分区：
文献类型：
--
作者：
Yasmin-Karim S;Bruck PT;Moreau M;Kunjachan S;Chen GZ;Kumar R;Grabow S;Dougan SK;Ngwa W
放射治疗诱导免疫原性细胞死亡，理论上可以刺激T细胞引发和诱导肿瘤特异性记忆T细胞应答，作为原位疫苗。在实践中，这种远位效应很少观察到。我们使用两种胰腺癌小鼠模型来证明单剂量立体定向体部放射治疗（SBRT）与肿瘤内注射激动性抗CD40协同作用，导致未治疗的对侧肿瘤消退和长期免疫记忆的形成。当小鼠接受SBRT的多个部分时，或当TGFβ阻断与SBRT组合时，未观察到长期存活。SBRT和抗CD40在增强T细胞引发方面是如此有效，以至于诱导了对肿瘤和自身抗原的记忆性CD8 T细胞应答，导致长期存活者患上白癜风。
Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an in situ vaccine. In practice, this abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a single dose of stereotactic body radiation therapy (SBRT) synergizes with intratumoral injection of agonistic anti-CD40, resulting in regression of non-treated contralateral tumors and formation of long-term immunologic memory. Long-term survival was not observed when mice received multiple fractions of SBRT, or when TGFβ blockade was combined with SBRT. SBRT and anti-CD40 was so effective at augmenting T cell priming, that memory CD8 T cell responses to both tumor and self-antigens were induced, resulting in vitiligo in long-term survivors.
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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
影响因子：
7.3
作者：
Dougan M
通讯作者：
Dougan M
影响因子：
8.8
作者：
Corrales L;Glickman LH;McWhirter SM;Kanne DB;Sivick KE;Katibah GE;Woo SR;Lemmens E;Banda T;Leong JJ;Metchette K;Dubensky TW Jr;Gajewski TF
通讯作者：
Gajewski TF
DOI：
10.1158/1078-0432.ccr-16-0870
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：
Kalbasi A;Komar C;Tooker GM;Liu M;Lee JW;Gladney WL;Ben-Josef E;Beatty GL
通讯作者：
Beatty GL
DOI：
10.1158/1078-0432.ccr-09-0265
发表时间：
2009-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dewan MZ;Galloway AE;Kawashima N;Dewyngaert JK;Babb JS;Formenti SC;Demaria S
通讯作者：
Demaria S