The role of IFN-γ-signalling in response to immune checkpoint blockade therapy.

IF 5.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Essays in biochemistry Pub Date : 2023-09-28 DOI:10.1042/EBC20230001

Chun Wai Wong, Yang Yu Huang, Adam Hurlstone

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Abstract

Treatment with immune checkpoint inhibitors, widely known as immune checkpoint blockade therapy (ICBT), is now the fourth pillar in cancer treatment, offering the chance of durable remission for patients with advanced disease. However, ICBT fails to induce objective responses in most cancer patients with still others progressing after an initial response. It is necessary, therefore, to elucidate the primary and acquired resistance mechanisms to ICBT to improve its efficacy. Here, we highlight the paradoxical role of the cytokine interferon-γ (IFN-γ) in ICBT response: on the one hand induction of IFN-γ signalling in the tumour microenvironment correlates with good ICBT response as it drives the cellular immune responses required for tumour destruction; nonetheless, IFN-γ signalling is implicated in ICBT acquired resistance. We address the negative feedback and immunoregulatory effects of IFN-γ signalling that promote immune evasion and resistance to ICBT and discuss how these can be targeted pharmacologically to restore sensitivity or circumvent resistance.

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IFN-γ信号传导在免疫检查点阻断治疗中的作用。

免疫检查点抑制剂治疗，即众所周知的免疫检查点阻断疗法（ICBT），目前是癌症治疗的第四大支柱，为晚期疾病患者提供了持久缓解的机会。然而，ICBT未能在大多数癌症患者中诱导客观反应，还有其他患者在最初反应后进展。因此，有必要阐明对ICBT的主要和后天耐药性机制，以提高其疗效。在这里，我们强调了细胞因子干扰素-γ（IFN-γ）在ICBT反应中的矛盾作用：一方面，在肿瘤微环境中诱导IFN-γ信号传导与良好的ICBT反应相关，因为它驱动肿瘤破坏所需的细胞免疫反应；尽管如此，IFN-γ信号传导与ICBT获得性耐药性有关。我们讨论了IFN-γ信号传导的负反馈和免疫调节作用，这些作用促进免疫逃避和对ICBT的耐药性，并讨论了如何在药理学上靶向这些作用，以恢复敏感性或规避耐药性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Essays in biochemistry 生物-生化与分子生物学

CiteScore

10.50

自引率

0.00%

发文量

105

审稿时长

>12 weeks

期刊介绍： Essays in Biochemistry publishes short, digestible reviews from experts highlighting recent key topics in biochemistry and the molecular biosciences. Written to be accessible for those not yet immersed in the subject, each article is an up-to-date, self-contained summary of the topic. Bridging the gap between the latest research and established textbooks, Essays in Biochemistry will tell you what you need to know to begin exploring the field, as each article includes the top take-home messages as summary points. Each issue of the journal is guest edited by a key opinion leader in the area, and whether you are continuing your studies or moving into a new research area, the Journal gives a complete picture in one place. Essays in Biochemistry is proud to publish Understanding Biochemistry, an essential online resource for post-16 students, teachers and undergraduates. Providing up-to-date overviews of key concepts in biochemistry and the molecular biosciences, the Understanding Biochemistry issues of Essays in Biochemistry are published annually in October.