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分子途径和细胞子集与与免疫相关肌心炎和肌炎重叠的不良临床结果相关

Bilal A Siddiqui¹, Nicolas L Palaskas², Sreyashi Basu³

¹Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Cancer immunology research

|May 20, 2024

概括

免疫检查点抑制剂的毒性,如心肌炎和肌炎,涉及细胞毒性T细胞和炎症性髓状细胞. 这些发现揭示了治疗这些严重不良事件的新目标.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
病理学病理学病理学

背景情况:

免疫检查点疗法 (ICTs) 可以导致严重的免疫相关不良事件 (irAEs),包括心肌炎和肌炎.
驱动这些毒性的潜在分子机制和免疫细胞种群尚未得到充分理解.

研究的目的:

研究免疫相关心肌炎和肌炎的细胞和分子格局.
确定潜在的治疗目标来管理ICT引起的毒性.

主要方法:

从接受ICT的患者心脏和骨肌肉活检的单细胞RNA测序.
免疫组织化学和自身抗体分析.

主要成果:

在这两种疾病中都发现了具有细胞毒性和疲劳标记的CD8+ T细胞.
鉴定出表达组织居民特征和FcγRIIIa (CD16a) 的髓状细胞.
炎症性髓状细胞 (IL1B+TNF+) 在心肌炎中富含,与严重程度和不良结果相关.
观察到IgG和补充激活 (C4d) 的证据,与自身抗体有关.

结论:

髓状细胞群在ICT诱导的心肌炎和肌肉炎中发挥着重要作用.
特定的炎症性髓子集和补体激活与严重的irAEs有关.
这些发现突出了开发治疗方法的新目标,以减轻与ICT有关的毒性.

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