Immune Profiling of Dermatologic Adverse Events from Checkpoint Blockade using Tissue Cyclic Immunofluorescence.
Immune Profiling of Dermatologic Adverse Events from Checkpoint Blockade using Tissue Cyclic Immunofluorescence.
复制标题
使用组织循环免疫荧光对检查点封锁引起的皮肤不良事件进行免疫分析。
DOI：
10.1101/2023.04.03.535435
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
LeBoeuf,NicoleR
中科院分区：
文献类型：
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作者：
Maliga,Zoltan;Kim,DanielY;Bui,Ai-TramN;Lin,Jia-Ren;Dewan,AnnaK;Murphy,GeorgeF;Nirmal,AjitJ;Lian,ChristineG;Sorger,PeterK;LeBoeuf,NicoleR
在这项研究中，我们展示了全片CyCIF（基于组织的循环免疫荧光）成像在免疫检查点抑制剂（ICI）诱导的皮肤不良事件（dAEs）中表征免疫细胞浸润的应用。我们分析了6例ici诱导的dAEs，包括类地衣、大疱性类天疱疮、牛皮癣和湿疹疹，比较了标准免疫组织化学（IHC）和CyCIF获得的免疫谱结果。我们的研究结果表明，CyCIF比IHC提供了更详细和精确的免疫细胞浸润单细胞特征，IHC依赖于病理学家的半定量评分。这项初步研究强调了CyCIF的潜力，通过揭示免疫细胞浸润的组织水平空间模式，促进我们对dAEs免疫环境的理解，允许更精确的表型区分和更深入的疾病机制探索。通过证明CyCIF可以在脆弱组织（如大疱性类天疱疮）上进行，我们为未来的研究提供了基础，通过更大的表型毒性队列来检查特定dAEs的驱动因素，并建议高度多重组织成像在免疫介导的疾病表型中发挥更广泛的作用。
In this study, we demonstrate the utility of whole-slide CyCIF (tissue-based cyclic immunofluorescence) imaging for characterizing immune cell infiltrates in immune checkpoint inhibitor (ICI)-induced dermatologic adverse events (dAEs). We analyzed six cases of ICI-induced dAEs, including lichenoid, bullous pemphigoid, psoriasis, and eczematous eruptions, comparing immune profiling results obtained using both standard immunohistochemistry (IHC) and CyCIF. Our findings indicate that CyCIF provides more detailed and precise single-cell characterization of immune cell infiltrates than IHC, which relies on semi-quantitative scoring by pathologists. This pilot study highlights the potential of CyCIF to advance our understanding of the immune environment in dAEs by revealing tissue-level spatial patterns of immune cell infiltrates, allowing for more precise phenotypic distinctions and deeper exploration of disease mechanisms. By demonstrating that CyCIF can be performed on friable tissues, such as bullous pemphigoid, we provide a foundation for future studies to examine the drivers of specific dAEs using larger cohorts of phenotyped toxicity and suggest a broader role for highly multiplexed tissue imaging in phenotyping the immune mediated disease that they resemble.