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Nature:癌症免疫疗法新发现:阻断一种蛋白,让肿瘤明显缩小

2018-06-29 小通 生物通

免疫疗法在许多癌症类型中显示出很大的希望,但迄今为止,它们在前列腺癌中的作用仅限于一小部分男性。这项新研究发现了一种全新的方法来修改免疫系统以对抗前列腺癌。

免疫疗法在许多癌症类型中显示出很大的希望,但迄今为止,它们在前列腺癌中的作用仅限于一小部分男性。这项新研究发现了一种全新的方法来修改免疫系统以对抗前列腺癌。

一组研究人员发现,针对晚期前列腺癌患者,利用一种新的免疫疗法可以重新激活患者对激素治疗的反应,这在小鼠和人类前列腺癌细胞实验中得到了证实。研究人员认为,这与既有的治疗方法相结合可以改善前列腺癌的预后。

这一研究成果公布在6月27日的Nature杂志上。

激素疗法(Hormone therapy)是前列腺癌治疗的中流砥柱,但是经过治疗,肿瘤细胞会发展出耐药性,导致疾病难以进一步治疗。

这项新研究发现,阻断由一类免疫细胞:称为髓样抑制细胞(Myeloid-derived suppressor cells,MDSCs)产生的蛋白,能恢复肿瘤对激素治疗的敏感性。这种蛋白即IL-23,其实已经被用于了自身免疫性疾病,如牛皮癣等的治疗中。

阻断IL-23,肿瘤缩小

伦敦癌症研究所的与瑞士癌症研究所的研究人员一道,采集了前列腺癌患者的肿瘤和血液样本,希望能了解髓样抑制细胞在前列腺癌中的作用。

他们发现,比较于依然对激素治疗有反应的患者,患有耐药性前列腺癌的患者的血液和肿瘤样本中,这种抑制细胞和IL-23含量水平更高。

并且当研究人员分析不再产生IL-23的前列腺癌的小鼠时,他们发现小鼠的肿瘤显着萎缩,癌细胞生长得更慢。前列腺肿瘤对激素治疗耐药性出现也需要更长的时间,并且小鼠存活的时间更长。

阻断IL-23和阻止抑制细胞进入肿瘤,能帮助改善对激素治疗的反应,由此研究人员相信他们找到了驱动前列腺癌激素治疗抗性的关键机制。

他们指出,IL-23允许前列腺癌细胞避开雄激素激素的需求来促进其生长。

激素疗法与免疫疗法

癌症免疫疗法通过重新激活免疫系统,识别和杀死癌细胞发挥作用,在前列腺癌治疗中显示出一定的前景,但只有一部分男性对此反应良好。

而对于已经扩散到腺体以外的前列腺癌的治疗,经常会改变男性的激素平衡。由于睾酮具有促进前列腺生长的作用,所以激素疗法的目的就是要防止癌细胞和正常前列腺组织接受男性激素的刺激。但激素疗法只对前列腺癌起一个缓解作用,不能进行根治。

伦敦癌症研究学会Johann de Bono教授表示,“激素疗法在男性前列腺癌中效果很好,但是当癌症发展成为对治疗产生抵抗时,其它选择会大大减少。”

“我们的研究发现激素信号与免疫系统之间存在重要的相互作用,我们相信我们可以利用这一点来逆转前列腺癌中的激素耐药性,并增强广泛使用的前列腺癌药物,如enzalutamide的疗效。”

“我们希望能开展临床试验,研究如何将这种新型免疫疗法与现有的激素疗法结合起来,改善晚期前列腺癌患者的治疗。”

另外一位作者,IOR癌症研究所的Andrea Alimonti教授也解释到,“当我们发现产生IL23的MDSCs是激素治疗产生抗性的主要前列腺癌免疫细胞亚型时,我们立即意识到这些细胞可能是导致治疗抗性出现的原因之一。”

“这项研究描述了一种新的作用机制,通过这种机制,肿瘤免疫应答会支持前列腺癌的生长,这为将来转移性前列腺癌患者的新型治疗应用开辟了道路。”

免疫疗法在许多癌症类型中显示出很大的希望,但迄今为止,它们在前列腺癌中的作用仅限于一小部分男性。这项新研究发现了一种全新的方法来修改免疫系统以对抗前列腺癌。

激素疗法与这种新型免疫疗法的结合可能是一种令人兴奋的治疗晚期前列腺癌的新途径。

原始出处:Arianna Calcinotto, Clarissa Spataro, Elena Zagato, et al. IL-23 secreted by myeloid cells drives castration-resistant prostate cancer. Nature (2018) 

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    2019-04-25 liye789132251
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    2018-06-29 kafei

    学习学习谢谢

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    2018-06-29 龙胆草

    学习谢谢分享

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