Translational Immunology Laboratory, Department of Immunology, Institut Pasteur, F-75015 Paris, France.
Université de Paris, APHP Hôpital Saint-Louis, Dermatology Department, DMU ICARE, INSERM U-976, Paris, France.
Sci Adv. 2021 Aug 18;7(34). doi: 10.1126/sciadv.abg4081. Print 2021 Aug.
The COVID-19 pandemic has spread worldwide, yet the role of antiviral T cell immunity during infection and the contribution of immune checkpoints remain unclear. By prospectively following a cohort of 292 patients with melanoma, half of which treated with immune checkpoint inhibitors (ICIs), we identified 15 patients with acute or convalescent COVID-19 and investigated their transcriptomic, proteomic, and cellular profiles. We found that ICI treatment was not associated with severe COVID-19 and did not alter the induction of inflammatory and type I interferon responses. In-depth phenotyping demonstrated expansion of CD8 effector memory T cells, enhanced T cell activation, and impaired plasmablast induction in ICI-treated COVID-19 patients. The evaluation of specific adaptive immunity in convalescent patients showed higher spike (S), nucleoprotein (N), and membrane (M) antigen-specific T cell responses and similar induction of spike-specific antibody responses. Our findings provide evidence that ICI during COVID-19 enhanced T cell immunity without exacerbating inflammation.
新型冠状病毒肺炎疫情在全球范围内蔓延，但感染期间抗病毒 T 细胞免疫的作用以及免疫检查点的贡献仍不清楚。通过前瞻性随访 292 名黑色素瘤患者队列，其中一半接受免疫检查点抑制剂 (ICI) 治疗，我们确定了 15 名急性或恢复期新型冠状病毒肺炎患者，并对其进行了转录组、蛋白质组和细胞特征分析。我们发现 ICI 治疗与严重新型冠状病毒肺炎无关，也不会改变炎症和 I 型干扰素反应的诱导。深入表型分析表明，ICI 治疗的新型冠状病毒肺炎患者中 CD8 效应记忆 T 细胞扩增、T 细胞激活增强和浆母细胞诱导受损。对恢复期患者特异性适应性免疫的评估显示，刺突 (S)、核衣壳蛋白 (N) 和膜 (M) 抗原特异性 T 细胞反应更高，刺突特异性抗体反应的诱导也相似。我们的研究结果提供了证据，表明新型冠状病毒肺炎期间 ICI 增强了 T 细胞免疫，而没有加重炎症。
