GM-CSF and IL-7 fusion cytokine engineered tumor vaccine generates long-term Th-17 memory cells and increases overall survival in aged syngeneic mouse models of glioblastoma.
GM-CSF and IL-7 fusion cytokine engineered tumor vaccine generates long-term Th-17 memory cells and increases overall survival in aged syngeneic mouse models of glioblastoma.
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DOI：
10.1111/acel.13864
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发表时间：
2023-07
期刊：
影响因子：
7.8
通讯作者：
Dey, Mahua
中科院分区：
文献类型：
--
作者：
Shireman, Jack M.;Gonugunta, Nikita;Zhao, Lei;Pattnaik, Akshita;Distler, Emily;Her, Skyler;Wang, Xiaohu;Das, Rahul;Galipeau, Jaques;Dey, Mahua
年龄相关的免疫功能障碍，如T细胞输出减少，与老年人的癌症等病理和缺乏疫苗效力密切相关。GIFT‐7是白细胞介素7 （IL‐7）和GM‐CSF的融合产物，可以逆转衰老相关的淋巴器官萎缩。我们制备了一种GIFT‐7 fusokine肿瘤疫苗，并将其用于老年同基因小鼠胶质母细胞瘤模型，发现GIFT‐7TVax外周疫苗可导致胸腺再生，并在老年小鼠中产生持久的长期抗肿瘤免疫。整体细胞因子分析显示，在接种疫苗组中，包括IL - 1β在内的促炎细胞因子增加，导致树突状细胞过度活化。此外，GIFT - 7疫苗可增加T细胞向大脑的运输，增强Th - 17长期效应记忆T细胞的形成。TCR - seq分析显示，接种组中检测到的重排的生产频率增加。总的来说，我们的数据表明，衰老的免疫系统可以通过治疗增强来产生持久的抗肿瘤免疫。外周接种GIFT - 7 fusokine可诱导胸腺再生、树突状细胞超激活和T细胞转运到大脑。基于Th - 17的效应免疫的形成导致对侧颅内肿瘤再攻击的排斥反应，并证明了外周免疫增强老年免疫系统的有效性。
Age‐related immune dysfunctions, such as decreased T‐cell output, are closely related to pathologies like cancers and lack of vaccine efficacy among the elderly. Engineered fusokine, GIFT‐7, a fusion of interleukin 7 (IL‐7) and GM‐CSF, can reverse aging‐related lymphoid organ atrophy. We generated a GIFT‐7 fusokine tumor vaccine and employed it in aged syngeneic mouse models of glioblastoma and found that peripheral vaccination with GIFT‐7TVax resulted in thymic regeneration and generated durable long‐term antitumor immunity specifically in aged mice. Global cytokine analysis showed increased pro‐inflammatory cytokines including IL‐1β in the vaccinated group that resulted in hyperactivation of dendritic cells. In addition, GIFT‐7 vaccination resulted in increased T‐cell trafficking to the brain and robust Th‐17 long‐term effector memory T‐cell formation. TCR‐seq analysis showed increased productive frequency among detected rearrangements within the vaccinated group. Overall, our data demonstrate that aging immune system can be therapeutically augmented to generate lasting antitumor immunity. Peripheral vaccination with the GIFT‐7 fusokine induces thymic regeneration, dendritic cell hyper‐activation, and T‐cell trafficking to the brain. Formation of Th‐17 based effector immunity results in rejection of contralateral intracranial tumor re‐challenge and demonstrates the effectiveness of augmenting the aged immune system with peripheral vaccination.
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中枢神经系统自身免疫和肿瘤中的Type17 T细胞。
影响因子：
9.1
作者：
Okada, Hideho;Khoury, Samia J.
通讯作者：
Khoury, Samia J.
影响因子：
17.1
作者：
Boraschi, Diana;Aguado, M. Teresa;Del Giudice, Giuseppe
通讯作者：
Del Giudice, Giuseppe
胸腺基质细胞：在胸腺萎缩和年龄相关功能障碍中的作用。
影响因子：
3.9
作者：
Cepeda S;Griffith AV
通讯作者：
Griffith AV
DOI：
10.4049/jimmunol.182.2.784
发表时间：
2009-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ahmed M;Lanzer KG;Yager EJ;Adams PS;Johnson LL;Blackman MA
通讯作者：
Blackman MA
影响因子：
8
作者：
Alban, Tyler J.;Alvarado, Alvaro G.;Lathia, Justin D.
通讯作者：
Lathia, Justin D.