2018年诺贝尔生理学或医学奖授予抑制负性免疫调节的癌症治疗

Fukumi Furukawa
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引用次数: 23

摘要

10月1日,2018年诺贝尔生理学或医学奖被联合授予詹姆斯·p·艾利森博士和本庶佑博士,以表彰他们发现了通过抑制负性免疫调节来治疗癌症的方法。卡罗林斯卡研究所的诺贝尔大会发表评论说,Allison博士和Honjo博士展示了如何使用不同的策略来抑制免疫系统的刹车,从而可以用于治疗癌症[1-5]。两位获奖者的开创性发现在我们与癌症的斗争中具有里程碑意义。https://www.nobelprize.org/prizes/medicine/2018/prize-announcement/I衷心祝贺两位获奖者、同事以及合作临床试验的众多患者。到目前为止,我们在该杂志上发表了几篇关于免疫检查点的综述和论文。原因是这本杂志的使命是科学意识和传播新的免疫疗法。我在此简要介绍我之前的报告,并做了一些修改[6]。免疫检查点抑制剂(ICIs)在癌症治疗中开辟了有希望的途径。多种靶向程序性细胞死亡-1 (PD-1)和细胞毒性t淋巴细胞相关蛋白4 (CTLA-4)的阻断抗体已被批准用于人类。它们通过增强抗肿瘤免疫反应,显著改善了许多癌症患者的疾病预后。正如Seidel、Otsuka和Kabashima在他们的综述文章[7]中所述,在目前的治疗下,晚期患者的死亡率和治疗相关不良事件的发生率仍然很高。而且,同样值得注意的是,即使在对许多癌症患者进行治疗变得更好时,也会出现意想不到的免疫相关不良反应(irAEs)[8]。不幸的是,ICIs引起内分泌irae的机制尚不清楚,irae的最佳预防、预测和治疗仍不确定。然而,在皮肤病学[9]和其他器官[6,7]等许多领域,与预后相关的适当用途和指标设置正在进行研究。在解决这些问题的同时,我们必须明白,免疫原性细胞死亡的机制现在正从概念走向临床。我们将解释ICD背后的机制,以及它如何可能为癌症化疗的使用注入新的生命,不是前沿和中心,而是作为免疫治疗的得力助手[10]。很长一段时间以来,许多科学家和医生都试图利用免疫系统来对抗癌症。许多临床医生盯着即将在他们身边死去的癌症患者,哀悼他们的无能。然而,通过抑制负免疫调节检查点疗法的癌症治疗已经从根本上改变了我们看待癌症如何管理的方式,许多患者将得到更好的护理和治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Nobel Prize in Physiology or Medicine 2018 was awarded to Cancer Therapy by Inhibition of Negative Immune Regulation
   On October 1, The Nobel Prize in Physiology or Medicine 2018 was awarded jointly to Dr. James P. Allison and Dr. Tasuku Honjo "for their discovery of cancer therapy by inhibition of negative immune regulation.The Nobel Assembly at Karolinska Institute released the comments that Dr. Allison and Dr. Honjo showed how different strategies for inhibiting the brakes on the immune system could be used in the treatment of cancer [1-5]. The seminal discoveries by the two laureates constitute a landmark in our fight against cancer. https://www.nobelprize.org/prizes/medicine/2018/prize-announcement/I sincerely wish to congratulate two recipients, co-workers and many patients cooperated in clinical trials. In this journal, we have published several reviews and papers on immunity checkpoints so far. The reason is that the mission of this journal is in scientific awareness and dissemination of new immunotherapy.I herein introduce briefly my previous report with some modification [6]. Immune checkpoints inhibitors (ICIs) have opened promising avenues in the treatment of cancer. Various blocking antibodies targeting programmed cell death -1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are approved for human use. They significantly improved disease outcome in a number of cancer patients by boosting anti-tumor immune responses. As Seidel, Otsuka and Kabashima described in their review article [7], mortality among advanced stage patients and the frequency of treatment-related adverse events remain high with current treatment. And, it is also noteworthy that unexpected immune related adverse effects (irAEs) appear, even when it becomes better to be administered to many cancer patients [8]. Unfortunately, the mechanisms of endocrine irAEs by ICIs, remain unclear, and optimal prevention, prediction, and treatment of the irAEs are still uncertain. However, appropriate uses and index setting related to prognosis are being studied in many fields such as dermatology [9] and other organs [6,7].While solving such problems, we have to understand that the mechanisms of immunogenic cell death are now moving from concepts to the clinic. We will explain the mechanism behind ICD and how it will perhaps breathe a new life into chemotherapy use in cancer, not front and center but as a helpful hand to immunotherapy [10].For a long time many scientists or doctors attempted to engage the immune system in the fight against cancer. Many clinicians stared at cancer patients who were to be dying by their side, mourning their inability. However, cancer therapy by inhibition of negative immune regulation checkpoint therapy has fundamentally changed the way we view how cancer can be managed and many patients will receive much better care and cure. 
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