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腾讯登录PNAS：TNF-α在肿瘤中作用机制
| 导读 | <div>
近日，西澳大利亚医学研究所的科学家取得了令人振奋的研究进展，他们利用人体自身的免疫系统帮助患者与癌症作斗争，研究论文发表在PNAS杂志上。
到现在为止，免疫治疗在癌症治疗方面未获得成功，因为肿瘤有抗免疫细胞功能。
肿瘤细胞的生长过程中会形成一个实心球，免疫细胞很难进入肿瘤组织内部，即使免疫细胞可以穿透肿瘤，但肿瘤组织内部的环境会杀死免疫细胞，是使得免疫细胞... |
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近日，西澳大利亚医学研究所的科学家取得了令人振奋的研究进展，他们利用人体自身的免疫系统帮助患者与癌症作斗争，研究论文发表在PNAS杂志上。
到现在为止，免疫治疗在癌症治疗方面未获得成功，因为肿瘤有抗免疫细胞功能。
肿瘤细胞的生长过程中会形成一个实心球，免疫细胞很难进入肿瘤组织内部，即使免疫细胞可以穿透肿瘤，但肿瘤组织内部的环境会杀死免疫细胞，是使得免疫细胞难以发挥功效使。
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研究人员设计的一种蛋白质叫做肿瘤坏死因子-α，这一因子可直接进入胰腺肿瘤组织内部，同时对肿瘤周围组织无毒副作用。
肿瘤坏死因子-α影响肿瘤组织内部的血管，使免疫细胞能够进入肿瘤内部。
TNF-α已被证明能提高肿瘤的化疗反应，但到现在为止科学家不明白其中机制。这项研究首次揭示了低剂量TNF-α在肿瘤中是如何发挥作用的，其增强化疗反应的作用或许与免疫有关。
<br/><strong>原文摘要：</strong><br/>
<p align="center"><br/><strong>Tumor-targeted TNFα stabilizes tumor vessels and enhances active immunotherapy</strong><br/>
</p>
<p align="center">Anna Johanssona, Juliana Hamzahb, Christine J. Paynea, and Ruth Ganssa</p>
Solid tumors are intrinsically resistant to immune rejection. Abnormal tumor vasculature can act as a barrier for immune cell migration into tumors. We tested whether targeting IFNγ and/or TNFα into pancreatic neuroendocrine tumors can alleviate immune suppression. We found that intratumoral IFNγ causes rapid vessel loss, which does not support anti-tumor immunity. In contrast, low-dose TNFα enhances T-cell infiltration and overall survival, an effect that is exclusively mediated by CD8+ effector cells. Intriguingly, lymphocyte influx does not correlate with increased vessel leakiness. Instead, low-dose TNFα stabilizes the vascular network and improves vessel perfusion. Inflammatory vessel remodeling is, at least in part, mediated by tumor-resident macrophages that are reprogrammed to secrete immune and angiogenic modulators. Moreover, inflammatory vessel remodeling with low-dose TNFα substantially improves antitumor vaccination or adoptive T-cell therapy. Thus, low-dose TNFα promotes both vessel remodeling and antitumor immune responses and acts as a potent adjuvant for active immunotherapy.
</div>
近日，西澳大利亚医学研究所的科学家取得了令人振奋的研究进展，他们利用人体自身的免疫系统帮助患者与癌症作斗争，研究论文发表在PNAS杂志上。
到现在为止，免疫治疗在癌症治疗方面未获得成功，因为肿瘤有抗免疫细胞功能。
肿瘤细胞的生长过程中会形成一个实心球，免疫细胞很难进入肿瘤组织内部，即使免疫细胞可以穿透肿瘤，但肿瘤组织内部的环境会杀死免疫细胞，是使得免疫细胞难以发挥功效使。
<!--more-->
研究人员设计的一种蛋白质叫做肿瘤坏死因子-α，这一因子可直接进入胰腺肿瘤组织内部，同时对肿瘤周围组织无毒副作用。
肿瘤坏死因子-α影响肿瘤组织内部的血管，使免疫细胞能够进入肿瘤内部。
TNF-α已被证明能提高肿瘤的化疗反应，但到现在为止科学家不明白其中机制。这项研究首次揭示了低剂量TNF-α在肿瘤中是如何发挥作用的，其增强化疗反应的作用或许与免疫有关。
<br/><strong>原文摘要：</strong><br/>
<p align="center"><br/><strong>Tumor-targeted TNFα stabilizes tumor vessels and enhances active immunotherapy</strong><br/>
</p>
<p align="center">Anna Johanssona, Juliana Hamzahb, Christine J. Paynea, and Ruth Ganssa</p>
Solid tumors are intrinsically resistant to immune rejection. Abnormal tumor vasculature can act as a barrier for immune cell migration into tumors. We tested whether targeting IFNγ and/or TNFα into pancreatic neuroendocrine tumors can alleviate immune suppression. We found that intratumoral IFNγ causes rapid vessel loss, which does not support anti-tumor immunity. In contrast, low-dose TNFα enhances T-cell infiltration and overall survival, an effect that is exclusively mediated by CD8+ effector cells. Intriguingly, lymphocyte influx does not correlate with increased vessel leakiness. Instead, low-dose TNFα stabilizes the vascular network and improves vessel perfusion. Inflammatory vessel remodeling is, at least in part, mediated by tumor-resident macrophages that are reprogrammed to secrete immune and angiogenic modulators. Moreover, inflammatory vessel remodeling with low-dose TNFα substantially improves antitumor vaccination or adoptive T-cell therapy. Thus, low-dose TNFα promotes both vessel remodeling and antitumor immune responses and acts as a potent adjuvant for active immunotherapy.
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