近日,，西澳大利亞醫(yī)學(xué)研究所的科學(xué)家取得了令人振奮的研究進(jìn)展,，他們利用人體自身的免疫系統(tǒng)幫助患者與癌癥作斗爭(zhēng),，研究論文發(fā)表在PNAS雜志上,。
到現(xiàn)在為止,，免疫治療在癌癥治療方面未獲得成功,，因?yàn)槟[瘤有抗免疫細(xì)胞功能。
腫瘤細(xì)胞的生長(zhǎng)過(guò)程中會(huì)形成一個(gè)實(shí)心球,，免疫細(xì)胞很難進(jìn)入腫瘤組織內(nèi)部,，即使免疫細(xì)胞可以穿透腫瘤,，但腫瘤組織內(nèi)部的環(huán)境會(huì)殺死免疫細(xì)胞，是使得免疫細(xì)胞難以發(fā)揮功效使,。
研究人員設(shè)計(jì)的一種蛋白質(zhì)叫做腫瘤壞死因子-α,，這一因子可直接進(jìn)入胰腺腫瘤組織內(nèi)部，同時(shí)對(duì)腫瘤周圍組織無(wú)毒副作用,。
腫瘤壞死因子-α影響腫瘤組織內(nèi)部的血管,，使免疫細(xì)胞能夠進(jìn)入腫瘤內(nèi)部。
TNF-α已被證明能提高腫瘤的化療反應(yīng),，但到現(xiàn)在為止科學(xué)家不明白其中機(jī)制,。這項(xiàng)研究首次揭示了低劑量TNF-α在腫瘤中是如何發(fā)揮作用的，其增強(qiáng)化療反應(yīng)的作用或許與免疫有關(guān),。 （生物谷：Bioon.com）
doi:10.1073/pnas.1118296109
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PMID:
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.
