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实体瘤的免疫景观:肿瘤与自身免疫的相互作用。

Immunological landscape of solid cancer: Interplay between tumor and autoimmunity.

机构信息

Department of Oncology, Albert Einstein College of Medicine, Bronx, NY, United States; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, United States.

Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, United States.

出版信息

Int Rev Cell Mol Biol. 2024;389:163-235. doi: 10.1016/bs.ircmb.2024.04.002. Epub 2024 May 31.

DOI:10.1016/bs.ircmb.2024.04.002
PMID:39396847
Abstract

The immune system, a central player in maintaining homeostasis, emerges as a pivotal factor in the pathogenesis and progression of two seemingly disparate yet interconnected categories of diseases: autoimmunity and cancer. This chapter delves into the intricate and multifaceted role of the immune system, particularly T cells, in orchestrating responses that govern the delicate balance between immune surveillance and self-tolerance. T cells, pivotal immune system components, play a central role in both diseases. In autoimmunity, aberrant T cell activation drives damaging immune responses against normal tissues, while in cancer, T cells exhibit suppressed responses, allowing the growth of malignant tumors. Immune checkpoint receptors, example, initially explored in autoimmunity, now revolutionize cancer treatment via immune checkpoint blockade (ICB). Though effective in various tumors, ICB poses risks of immune-related adverse events (irAEs) akin to autoimmunity. This chapter underscores the importance of understanding tumor-associated antigens and their role in autoimmunity, immune checkpoint regulation, and their implications for both diseases. It also explores autoimmunity resulting from cancer immunotherapy and shared molecular pathways in solid tumors and autoimmune diseases, highlighting their interconnectedness at the molecular level. Additionally, it sheds light on common pathways and epigenetic features shared by autoimmunity and cancer, and the potential of repurposing drugs for therapeutic interventions. Delving deeper into these insights could unlock therapeutic strategies for both autoimmunity and cancer.

摘要

免疫系统是维持体内平衡的核心因素,它在自身免疫性疾病和癌症这两类看似截然不同但又相互关联的疾病的发病机制和进展中起着关键作用。本章深入探讨了免疫系统,特别是 T 细胞,在协调免疫监视和自身耐受之间微妙平衡的反应中所扮演的复杂而多面的角色。T 细胞作为免疫系统的关键组成部分,在这两种疾病中都起着核心作用。在自身免疫性疾病中,异常的 T 细胞激活会引发针对正常组织的破坏性免疫反应,而在癌症中,T 细胞的反应受到抑制,从而允许恶性肿瘤的生长。免疫检查点受体最初在自身免疫性疾病中得到探索,现在通过免疫检查点阻断(ICB)彻底改变了癌症治疗。尽管在各种肿瘤中有效,但 ICB 会引发类似于自身免疫性疾病的免疫相关不良反应(irAEs)。本章强调了理解肿瘤相关抗原及其在自身免疫、免疫检查点调节中的作用以及它们对这两种疾病的影响的重要性。它还探讨了癌症免疫治疗引起的自身免疫以及实体瘤和自身免疫性疾病中共同的分子途径,强调了它们在分子水平上的相互关联性。此外,还揭示了自身免疫和癌症之间共同的途径和表观遗传特征,以及重新利用药物进行治疗干预的潜力。深入研究这些见解可能为自身免疫和癌症的治疗策略提供新的思路。

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Immunological landscape of solid cancer: Interplay between tumor and autoimmunity.实体瘤的免疫景观:肿瘤与自身免疫的相互作用。
Int Rev Cell Mol Biol. 2024;389:163-235. doi: 10.1016/bs.ircmb.2024.04.002. Epub 2024 May 31.
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A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity.关于共刺激受体和 Treg 稳态在自身免疫和肿瘤免疫中的作用的全面综述。
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Cancer immunotherapy with check point inhibitor can cause autoimmune adverse events due to loss of Treg homeostasis.癌症免疫疗法中的检查点抑制剂可能会由于 Treg 稳态的丧失而导致自身免疫性不良反应。
Semin Cancer Biol. 2020 Aug;64:29-35. doi: 10.1016/j.semcancer.2019.01.006. Epub 2019 Feb 1.
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A Threshold Model for T-Cell Activation in the Era of Checkpoint Blockade Immunotherapy.在检查点阻断免疫治疗时代的 T 细胞激活的阈值模型。
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Understanding adverse events of immunotherapy: A mechanistic perspective.理解免疫治疗的不良反应:一种机制观点。
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Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: A review.自身免疫、检查点抑制剂治疗和免疫相关不良事件:综述。
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Exploiting autoimmunity unleashed by low-dose immune checkpoint blockade to treat advanced cancer.利用低剂量免疫检查点阻断引发的自身免疫来治疗晚期癌症。
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Balancing cancer immunotherapy and immune-related adverse events: The emerging role of regulatory T cells.平衡癌症免疫疗法和免疫相关不良事件:调节性 T 细胞的新作用。
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Immunol Rev. 2023 Sep;318(1):89-95. doi: 10.1111/imr.13238. Epub 2023 Jul 8.

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