Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.
Cell. 2019 Sep 5;178(6):1493-1508.e20. doi: 10.1016/j.cell.2019.08.008. Epub 2019 Aug 29.
Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.
细胞因子阻断在回肠克罗恩病 (iCD) 中的临床获益仅限于一部分患者。在这里，我们应用单细胞技术来研究 iCD 病变，以探讨细胞异质性是否导致治疗抵抗。我们发现，一部分患者在炎症组织中表达了一个独特的细胞模块，该模块由 IgG 浆细胞、炎症性单核吞噬细胞、活化的 T 细胞和基质细胞组成，我们将其命名为 GIMATS 模块。配体-受体相互作用对的分析确定了一个独特的网络连接，可能驱动 GIMATS 模块。引人注目的是，该 GIMATS 模块在另外四个独立的 iCD 队列中的一部分患者中也存在（n=441），并且在诊断时存在该模块与抗 TNF 治疗后无法实现持久的皮质类固醇自由缓解相关。这些结果强调了当前诊断检测的局限性，以及单细胞图谱工具识别治疗反应和个体化治疗机会的新型生物标志物的潜力。
