The role of immune checkpoint inhibitors in the development and treatment of infectious processes

Dilya A. Mustafina, Aisylu N. Bagautdinova, Milyausha M. Zinatullina, Diana I. Bukharmetova, NIkita A. Gorbunov, Elvina T. Zainetdinova, Daniil Yu. Leonov, Aibike G. Pirmagomedova, Anna E. Chernyshova, Maria P. Markhanos, Anna G. Abgaryan, Arina S. Arustamyan, Konstantin S. Chavro, Farzonakhon Mirzojonova
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Abstract

The incidence and prevalence of oncological diseases, which are in second place in terms of the frequency of causes of death, is steadily increasing among the population of the Russian Federation. Advances in translational medicine, including immunotherapy, have revolutionized cancer treatment strategies. A special breakthrough has been achieved in two areas of immunotherapy that have modernized cancer treatment: chimeric T-cell receptors and antibodies known as immune checkpoint inhibitors (ICTs) blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1) and ligand programmed cell death receptor (PD-L1). ICTs enhance the adaptive immune response of the tumor and can cause adverse effects as a result of hyperactivation of T cells, which often leads to the emergence of an opportunistic infection. In addition, immunosuppressive drugs, which are often prescribed to mitigate the side effects associated with ICT, are also a risk factor for infection. The purpose of the review is to analyze the literature on possible relationships between ICT inhibitors and the risk of infection, as well as to consider the possible benefits of ICT inhibitors as a treatment for various types of infections, including viral, parasitic and fungal, as well as sepsis. Although ICT inhibitors have demonstrated the ability to significantly prolong the life expectancy of patients with advanced cancer, they often lead to adverse events, which often requires treatment with immunosuppressive drugs, including corticosteroids, anti-TNF and other biological agents. The overall effect of ICT inhibitors on human infections remains poorly understood. Further research is needed to understand the basic mechanisms of the immunological effects of ICT inhibitors on various types of infections, which in some cases may be beneficial.
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免疫检查点抑制剂在感染过程的发展和治疗中的作用
在俄罗斯联邦人口中,肿瘤疾病的发病率和流行率正在稳步上升,在死亡原因中占第二位。转化医学(包括免疫疗法)的进步彻底改变了癌症治疗策略。免疫疗法的两个领域取得了特殊突破,使癌症治疗实现了现代化:嵌合 T 细胞受体和抗体,即免疫检查点抑制剂(ICTs),可阻断细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)、程序性细胞死亡蛋白-1(PD-1)和配体程序性细胞死亡受体(PD-L1)。信息和通信技术可增强肿瘤的适应性免疫反应,并可能因T细胞过度激活而产生不良反应,这往往会导致机会性感染的出现。此外,为减轻 ICT 的副作用而经常使用的免疫抑制剂也是感染的风险因素之一。本综述旨在分析 ICT 抑制剂与感染风险之间可能存在关系的文献,并考虑 ICT 抑制剂作为治疗病毒、寄生虫和真菌等各类感染以及败血症的药物可能带来的益处。尽管 ICT 抑制剂已证明能够显著延长晚期癌症患者的预期寿命,但它们往往会导致不良反应,这通常需要使用免疫抑制剂治疗,包括皮质类固醇、抗肿瘤坏死因子和其他生物制剂。人们对 ICT 抑制剂对人类感染的总体影响仍然知之甚少。需要进一步研究,以了解 ICT 抑制剂对各种类型感染的免疫效应的基本机制,在某些情况下,这种效应可能是有益的。
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