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肿瘤内杂乱DNA可能妨碍癌症免疫疗法

王彦 发布于 2017-02-07 16:35:01

根据美国的科学家,利用免疫系统的力量来治疗癌症可能在肿瘤携带不正确包装的DNA患者中不太奏效。

这个研究成果发表在《科学》期刊上,也许有一天能够帮助医生来决定那种类型的患者能够从免疫疗法中受益。

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“这可能导致靶向引起患者生存率低下的人类癌症的特色方法,” - Charles Swanton教授说

我们的免疫系统保护我们免受一系列疾病,但癌症通常可以避免检测和破坏。

这个新研究表明,DNA数量的错误和它在癌细胞里面如何包装-叫做非整倍体-可能影响免疫系统的能力来毁坏肿瘤细胞。

“这些研究强有力的揭示了非整倍体通过免疫系统帮助肿瘤逃避检测,”由英国癌症研究院部分资助,来自伦敦弗朗西斯·克里克研究所的Charles Swanton教授说。促进免疫系统识别和靶向癌细胞的免疫疗法迅速成为癌症研究中令人激动的癌症研究领域之一。但不是每个病人都会对这种治疗做出反应。

哈佛医学院的研究人员通过研究大量的基因数据,现在已经发现了患者对免疫疗法如何反应和肿瘤细胞内DNA的错误是如何包装之间的潜在联系。

DNA,基因材料包含了细胞应如何工作的说明,打包成束叫做基因组。正常细胞有23对基因组,但是癌症细胞通常比这个魔法数字更多或更少。

研究人员查看了来自癌症基因组图谱(一个大型美国研究数据库)中的来自12种不同类型癌症的约5000个肿瘤样品的数据,他们发现在高水平的非整倍体的肿瘤中,告诉细胞生长和分裂的基因被更多地开启。

他们还发现这些肿瘤样品中的免疫细胞水平较低。这表明免疫系统不能检测或一如既往的与这些癌症作斗争。

下一步研究人员观察了2项以前的关于免疫治疗黑色素瘤(一种皮肤癌)的实验数据,称为检查点抑制剂。他们发现具有高水平非整倍体的肿瘤患者在治疗后没有活多久。

“这项工作表明,我们需要继续探索非整倍体是如何发生以及如何继续的,”Swanton补充说。

“如果我们能做到这一点,这就可能导致靶向引起患者生存率低下的人类癌症的特色方法。”

Scrambled DNA inside tumours might hinder cancer immunotherapy

Cancer treatments that harness the power of the immune system might be less effective in patients whose tumours carry incorrectly packaged DNA, according to US scientists.

The finding, published in the journal Science, might one day be used to help doctors decide which patients are most likely to benefit from immunotherapies.

"It might lead to ways of targeting this feature of human cancers which leads to such poor survival in patients" – Professor Charles Swanton

Our immune system protects us against a range of diseases, but cancers can often avoid detection and destruction.

The new study suggests that errors in the quantity of DNA and how it’s packaged inside cancer cells – called aneuploidy – might affect the immune system’s ability to destroy the cells.

“These findings strongly suggest that aneuploidy helps tumours evade detection by the immune system,” said Professor Charles Swanton,from the Francis Crick Institute in London, part-funded by Cancer Research UK.

Immunotherapies which boost the immune system to recognise and target cancer cells have quickly become one of the most exciting areas of cancer research. But not every patient will respond to these kinds of treatment.

By studying large sets of genetic data the researchers at Harvard Medical School have now uncovered a potential link between how well patients respond to immunotherapy and errors in how the DNA inside their tumour cells is packaged.

DNA,genetic material which contains the instructions for how cells should work, is packaged into bundles called chromosomes. Normal cells have 23 pairs of chromosomes, but cancer cells frequently have more or less than this magic number.

The researchers looked at data from around 5,000 tumour samples from 12 different kinds of cancer held in The Cancer Genome Atlas – a large US research database. They found that in tumours with high levels of aneuploidy, genes which tell a cell to grow and divide were switched on more.

They also found lower levels of immune cells in those tumour samples. This suggests that the immune system wasn’t able to detect or fight those cancers as well as it should.

The researchers next looked at data from 2 previous trials of a type of immunotherapy for melanoma (a kind of skin cancer) called checkpoint inhibitors. They saw that patients whose tumours had high levels of aneuploidy didn’t live for as long after treatment.

“This work suggests that we need to continue exploring how aneuploidy comes about and how it is maintained,” added Swanton.

“If we can do that, then it might lead to ways of targeting this feature of human cancers which leads to such poor survival in patients."

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