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。
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。 （生物谷：Bioon.com）
doi:10.1073/pnas.1118296109
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Tumor-targeted TNFα stabilizes tumor vessels and enhances active immunotherapy
Anna Johanssona, Juliana Hamzahb, Christine J. Paynea, and Ruth Ganssa
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.
