Immune-checkpoint inhibitors: long-term implications of toxicity.
Immune-checkpoint inhibitors: long-term implications of toxicity.
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DOI：
10.1038/s41571-022-00600-w
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Balko JM
中科院分区：
文献类型：
--
作者：
Johnson DB;Nebhan CA;Moslehi JJ;Balko JM
免疫检查点抑制剂（ICI）的发展预示着癌症治疗的新时代，使转移性疾病患者的长期生存成为可能，并在早期环境中提供新的治疗适应症。因此，描述接受ICI的长期影响变得越来越重要。存在大量证据描述这些药物的急性临床毒性，尽管慢性效应尚未得到很好的分类。尽管如此，新出现的证据表明，持续毒性可能比最初建议的更常见。这些慢性后遗症通常程度较低，可影响内分泌、血液流变学、肺、神经和其他器官系统。致死性毒性还包括一系列不同的临床表现，可能发生在0.4-1.2%的患者中。考虑到长期生存的可能性，这种风险是一个特别相关的考虑因素。最后，免疫检查点阻断对多种免疫过程的影响，包括动脉粥样硬化、心力衰竭、神经炎症、肥胖和高血压，尚未得到表征，但仍然是与癌症幸存者潜在相关的重要研究领域。在这篇综述中，我们描述了目前慢性免疫毒性的证据，以及这些影响对接受ICI的患者的长期影响。免疫检查点抑制剂（ICI）显著改善了晚期实体瘤患者的预后，包括亚组长期缓解的可能性。然而，长期随访数据显示，这些药物存在慢性毒性风险，可能对生活质量产生重要影响。在这篇综述中，作者描述了目前ICIs慢性毒性的证据水平及其对患者的影响免疫检查点抑制剂（ICIs）在越来越多的转移性癌症患者中产生持久的反应，并且越来越多地用于（新）辅助治疗。虽然急性毒性更常见，但慢性免疫相关不良事件（irAE）越来越多地被认识到，并可影响高达40%的患者。慢性irAE大多被归类为内分泌或流变学，但可以影响各种器官。其他具有长期相关性的问题包括致死性irAE（可能发生在0.4-1.2%的患者中）和重度irAE后的再激发。ICIs还可能影响其他免疫介导的过程（如动脉粥样硬化或神经炎症），尽管还需要更多的研究。
The development of immune-checkpoint inhibitors (ICIs) has heralded a new era in cancer treatment, enabling the possibility of long-term survival in patients with metastatic disease, and providing new therapeutic indications in earlier-stage settings. As such, characterizing the long-term implications of receiving ICIs has grown in importance. An abundance of evidence exists describing the acute clinical toxicities of these agents, although chronic effects have not been as well catalogued. Nonetheless, emerging evidence indicates that persistent toxicities might be more common than initially suggested. While generally low-grade, these chronic sequelae can affect the endocrine, rheumatological, pulmonary, neurological and other organ systems. Fatal toxicities also comprise a diverse set of clinical manifestations and can occur in 0.4–1.2% of patients. This risk is a particularly relevant consideration in light of the possibility of long-term survival. Finally, the effects of immune-checkpoint blockade on a diverse range of immune processes, including atherosclerosis, heart failure, neuroinflammation, obesity and hypertension, have not been characterized but remain an important area of research with potential relevance to cancer survivors. In this Review, we describe the current evidence for chronic immune toxicities and the long-term implications of these effects for patients receiving ICIs. Immune-checkpoint inhibitors (ICIs) have dramatically improved the outcomes of patients with advanced-stage solid tumours, including the potential for long-term remission in a subset. However, long-term follow-up data reveal a risk of chronic toxicities from these agents, which can have important quality-of-life implications. In this Review, the authors describe the current level of evidence of chronic toxicities of ICIs and their implications for patients Immune-checkpoint inhibitors (ICIs) produce durable responses in a growing number of patients with metastatic cancer, and are being used increasingly in (neo)adjuvant settings. Although acute toxicities are more common, chronic immune-related adverse events (irAEs) are increasingly recognized, and can affect up to 40% of patients. Chronic irAEs are mostly classed as endocrine or rheumatological, but can affect a diverse array of organs. Other issues with long-term relevance include fatal irAEs (which can occur in 0.4–1.2% of patients), and rechallenge after severe irAEs. ICIs could also affect other immune-mediated processes (such as atherosclerosis or neuroinflammation), although more studies are needed.
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影响因子：
27.4
作者：
Cappelli LC;Gutierrez AK;Baer AN;Albayda J;Manno RL;Haque U;Lipson EJ;Bleich KB;Shah AA;Naidoo J;Brahmer JR;Le D;Bingham CO 3rd
通讯作者：
Bingham CO 3rd
DOI：
10.1152/ajpgi.00040.2019
发表时间：
2020-02-01
影响因子：
4.5
作者：
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通讯作者：
Kennedy, Arion J.
影响因子：
82.9
作者：
Baruch, Kuti;Deczkowska, Aleksandra;Schwartz, Michal
通讯作者：
Schwartz, Michal
影响因子：
9
作者：
Cameron, JL;Riall, TS;Belcher, KA
通讯作者：
Belcher, KA
影响因子：
27.4
作者：
Belkhir, Rakiba;Le Burel, Sebastien;Mariette, Xavier
通讯作者：
Mariette, Xavier