Kickstarting Immunity in Cold Tumours: Localised Tumour Therapy Combinations With Immune Checkpoint Blockade.
Kickstarting Immunity in Cold Tumours: Localised Tumour Therapy Combinations With Immune Checkpoint Blockade.
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感冒肿瘤的启动免疫：局部肿瘤治疗与免疫检查点阻断相结合。
DOI：
10.3389/fimmu.2021.754436
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wennerberg E
中科院分区：
文献类型：
--
作者：
Appleton E;Hassan J;Chan Wah Hak C;Sivamanoharan N;Wilkins A;Samson A;Ono M;Harrington KJ;Melcher A;Wennerberg E
具有低或缺乏预先存在的抗肿瘤免疫力的癌症患者（“冷”肿瘤）对免疫检查点抑制剂（ICPI）的治疗反应较差。为了使这些患者对ICPI易感，需要启动从头肿瘤靶向免疫应答。这涉及触发炎症信号传导、先天免疫激活（包括树突状细胞（DC）的募集和刺激）以及最终引发肿瘤特异性T细胞。肿瘤局部化疗法触发这些途径并作为原位肿瘤疫苗的能力正在被越来越多地探索，期望开发与ICPI的联合策略，以产生持久的反应。在这项工作中，至关重要的是要考虑治疗诱导的肿瘤微环境（TME）变化如何既作为免疫刺激剂，又在某些情况下加剧免疫抵抗机制。临床前研究中日益完善的免疫监测和临床试验中治疗期间活检的分析为治疗诱导的反应生物标志物以及局部治疗和ICB之间最佳协同作用的可操作目标提供了深入了解。在这里，我们回顾了新的和实验性的局部治疗的免疫调节作用的研究，以及重新评估既定的治疗，如放疗，作为免疫佐剂，重点是ICPI组合。
Cancer patients with low or absent pre-existing anti-tumour immunity (“cold” tumours) respond poorly to treatment with immune checkpoint inhibitors (ICPI). In order to render these patients susceptible to ICPI, initiation of de novo tumour-targeted immune responses is required. This involves triggering of inflammatory signalling, innate immune activation including recruitment and stimulation of dendritic cells (DCs), and ultimately priming of tumour-specific T cells. The ability of tumour localised therapies to trigger these pathways and act as in situ tumour vaccines is being increasingly explored, with the aspiration of developing combination strategies with ICPI that could generate long-lasting responses. In this effort, it is crucial to consider how therapy-induced changes in the tumour microenvironment (TME) act both as immune stimulants but also, in some cases, exacerbate immune resistance mechanisms. Increasingly refined immune monitoring in pre-clinical studies and analysis of on-treatment biopsies from clinical trials have provided insight into therapy-induced biomarkers of response, as well as actionable targets for optimal synergy between localised therapies and ICB. Here, we review studies on the immunomodulatory effects of novel and experimental localised therapies, as well as the re-evaluation of established therapies, such as radiotherapy, as immune adjuvants with a focus on ICPI combinations.
影响因子：
7.2
作者：
Kono K;Mimura K
通讯作者：
Mimura K