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Targeting the complement system to improve radiation response

针对补体系统改善放射反应

基本信息

批准号：
MC_UU_00001/10
负责人：
Monica Olcina
金额：
$ 113.24万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Intramural
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MC_UU_00001%2F10
关键词：
Targeting complement system improve radiation

项目摘要

Our lab tries to understand how cancers exploit part of our immune system to their advantage. Our most recent work has focused on, the complement system, a part of the immune system that is best known for its role in helping fight infections. We have become very interested in this part of the immune system since cancer cells seem to hijack it for their own survival advantage. We are exploring the idea that cancer cells may be particularly dependent on these hijacked functions when exposed to external sources of damage, such as those used to kill the tumour during treatment. Our work indeed suggests that if we block certain parts of this system (with drugs) we may be able to make the cancer cell more likely to die following radiotherapy. Intriguingly, blocking certain parts of this system may also reduce the toxic effects of radiation in healthy gut. These findings therefore suggest that a drug against this system could reduce the side effects of radiation while also improving the effectiveness of radiotherapy on the tumour. We work to understand the details of how this works. The ultimate goal of these studies is to be able to use drugs against this system to improve radiotherapy in patients.

我们的实验室试图了解癌症是如何利用我们的免疫系统的一部分来获得优势的。我们最新的工作集中在补体系统上，补体系统是免疫系统的一部分，最著名的是它在帮助对抗感染方面的作用。我们对免疫系统的这一部分非常感兴趣，因为癌细胞似乎为了自己的生存优势而劫持了它。我们正在探索这样一种想法，即当癌细胞暴露在外部损害源中时，可能特别依赖于这些被劫持的功能，例如那些在治疗过程中用于杀死肿瘤的损害源。我们的工作确实表明，如果我们(用药物)阻断这个系统的某些部分，我们可能能够使癌细胞在放射治疗后更有可能死亡。有趣的是，阻断这一系统的某些部分也可能减少辐射对健康肠道的毒性影响。因此，这些发现表明，针对这一系统的药物可以减少辐射的副作用，同时还可以提高肿瘤的放射治疗效果。我们努力了解这是如何运作的细节。这些研究的最终目标是能够使用针对这一系统的药物来改善患者的放射治疗。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy

补体下调促进炎症特征，使结直肠癌对免疫治疗敏感

DOI：
10.5167/uzh-224692
发表时间：
2022
期刊：
影响因子：
0
作者：
Krieg, Carsten
通讯作者：
Krieg, Carsten

Replication catastrophe induced by cyclic hypoxia leads to increased APOBEC3B activity.

DOI：
10.1093/nar/gkab551
发表时间：
2021-07-21
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Bader SB;Ma TS;Simpson CJ;Liang J;Maezono SEB;Olcina MM;Buffa FM;Hammond EM
通讯作者：
Hammond EM

The Combination of Radiotherapy and Complement C3a Inhibition Potentiates Natural Killer cell Functions Against Pancreatic Cancer.

DOI：
10.1158/2767-9764.crc-22-0069
发表时间：
2022-07
期刊：
CANCER RESEARCH COMMUNICATIONS
影响因子：
0
作者：
Sodji, Quaovi H.;Nambiar, Dhanya K.;Viswanathan, Vignesh;von Eyben, Rie;Colburg, Deana;Binkley, Michael S.;Li, Caiyun G.;Olcina, Monica M.;Chang, Daniel T.;Le, Quynh-Thu;Giaccia, Amato J.
通讯作者：
Giaccia, Amato J.

Thinking inside the box: intracellular roles for complement system proteins come into focus.