Nat Med:手术前的免疫疗法对结肠癌有效

2020-04-08 竹子 转化医学网

导言:由于近几年免疫治疗相关的研究进展很多,去年ASCO大会上也探索了在结直肠癌中新辅助治疗的优化模式。研究人员积极思考,将其余结肠癌的术前治疗相联系,进行了NICHE研究,为非转移性结肠癌患者的治疗

导言:由于近几年免疫治疗相关的研究进展很多,去年ASCO大会上也探索了在结直肠癌中新辅助治疗的优化模式。研究人员积极思考,将其余结肠癌的术前治疗相联系,进行了NICHE研究,为非转移性结肠癌患者的治疗提供了新思路。

荷兰癌症研究所的研究人员进行了一项NICHE研究的新发现,是一项创新的II期临床试验。医学肿瘤学家Myriam Chalabi及其同事在4月6日将研究结果发表在《自然医学》杂志上。研究发现,患有结肠癌但远处无转移的患者可以在等待手术的同时接受短期免疫治疗,患者自身的免疫细胞可以在很短的时间内缩小或清除癌细胞。在患有特定亚型结肠癌(MSI)的患者中,有100%的患者从治疗中受益。MSS类型患者中有25%受益。

新辅助免疫疗法

手术前的免疫疗法称为新辅助免疫疗法。目的是在大肿瘤的情况下防止癌症复发或转移,从而使手术更加容易。该疗法的主要思想是在切除肿瘤之前使免疫系统熟悉所有肿瘤变异,使系统能够更好地响应。结肠癌是继黑色素瘤之后的第二种癌症,荷兰癌症研究所的研究人员已在科学期刊上证明了新辅助免疫疗法的作用,其他类型肿瘤的研究仍在进行中。

40名患有两种结肠癌亚型的患者参加了NICHE研究。其中有20个具有微卫星不稳定(MSI)亚型,这意味着该肿瘤高度易突变,会导致数百个突变。在所有非转移性结肠癌患者中,有15%患有这种类型,该疗法在所有20例患者中均有效。项目经理Myriam Chalabi说:“这个小组的缓解率很高。但是100%的利率是史无前例的。你不希望它会那么好。”

首次静脉给药后约四个星期,患者接受了手术。在那短时间内,绝大多数的肿瘤已完全或几乎完全清除。“我们可以清楚地看到肿瘤的位置,但患者自身的免疫细胞已经清除了癌细胞。”

先前的研究已经表明,免疫疗法可有效治疗这一亚组的晚期转移性结肠癌。有一个很好的科学解释:存在的新突变越多,肿瘤就越具有非自身性,从而促进免疫系统发挥作用。

“微卫星稳定”亚型结肠癌患者的缓解率为25%

NICHE研究中的其余20名患者患有微卫星稳定(MSS)肿瘤。相反,已知这种类型的肿瘤对免疫疗法反应不好。令他们惊讶的是,研究人员发现,这一组患者中有25%的反应也很好。鉴于所有非转移性结肠癌患者中有85%患有这种类型,这是一个有希望的结果。

研究人员正在实验室中的MSS组中寻找这种令人惊讶的高缓解率的解释。首先,这并不容易。Chalabi说:“我们调查了所有常见的犯罪嫌疑人,但这不是原因。例如,我们没有发现与黑色素瘤相同的预测因素。但是最终,我们确实找到了一种新的生物标志物。如果在后续研究中证明该标志物具有预测性,则可以提供一种简单的方法来鉴定患有黑色素瘤的患者。可以从免疫治疗中受益的MSS肿瘤。”

新辅助研究的一个重要的附加优势是,它们使免疫疗法对切除的癌组织的精确作用得以确定,具体针对各个患者。从这个意义上讲,随着实验室工作和临床实践的日益融合,新辅助疗法正在推动癌症研究的一场革命。

像NICHE这样的开拓性新辅助药物研究也对肿瘤外科医生的工作产生了重大影响。这些研究取决于他们的信任:外科医生是否愿意接受等待和不确定性?Myriam Chalabi说:“我们的外科医师从一开始就非常热情,否则我们将永远无法进行试验。” 因此,NICHE研究的首要目的是证明手术可以安全地,按计划进行,并且术后并发症不会比预期的多——事实确实如此。

可以免除手术吗?

与患者一样,研究人员对NICHE研究的结果感到非常满意。Chalabi说:“平均而言,大肿瘤平均在四周内缩小或完全清除是一个了不起的前所未有的结果。我们从未见过100%的缓解率。” 而一些患者在试验中提出的问题是,是否可以完全省去手术。

Chalabi警告说,这还为时过早,因为即使在手术时发现肿瘤已经消退,也不可能事先知道谁将做出完全反应,即使借助扫描也是如此。 因此,研究人员需要找到以下问题的答案:他们如何在手术前尽可能地了解患者是否会完全缓解?“这并不容易,但是我们正努力解决它。”

一旦肿瘤完全或几乎完全清除,患者仍然会发生转移的可能性是多少?Chalabi说:“我们认为风险非常低。我们已经发现了黑色素瘤。但是,首先,我们需要对患者进行治疗并对其进行监测,然后才能回答这个问题。”

因此,NICHE研究将继续进行,并将增加患者的数量,对他们进行至少三年的监视,以查看是否还有疾病。Chalabi说:“只有在那时,新疗法才能被视为标准疗法。” 同时,许多新的研究将在实验室中使用这些患者的肿瘤材料进行实验。研究人员将使用先进的医学成像技术和所谓的液体活检技术来寻找血液中肿瘤DNA的痕迹。

原始出处:

Myriam Chalabi, Lorenzo F. Fanchi, Krijn K. Dijkstra, et.al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nature Medicine 06 April 2020

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    2021-03-02 ms2000000050996988

    希望能扩大适应范围

    0

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    2021-03-02 ms2000000050996988

    有启发。

    0

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    2021-03-03 liye789132251
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    2020-08-18 lovetcm

    #结肠癌##新辅助免疫治疗#,是一个比较好的趋势。如果再结合化疗杀伤,可能作用更理想。只是化疗可能会影响到手术

    0

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    2020-04-10 ysr0321

    免疫新辅助治疗

    0

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    2020-04-10 智慧医人

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