Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cancer Cell. 2022 Jul 11;40(7):738-753.e5. doi: 10.1016/j.ccell.2022.05.013. Epub 2022 May 30.
How immune dysregulation affects recovery from COVID-19 infection in patients with cancer remains unclear. We analyzed cellular and humoral immune responses in 103 patients with prior COVID-19 infection, more than 20% of whom had delayed viral clearance. Delayed clearance was associated with loss of antibodies to nucleocapsid and spike proteins with a compensatory increase in functional T cell responses. High-dimensional analysis of peripheral blood samples demonstrated increased CD8 effector T cell differentiation and a broad but poorly converged COVID-specific T cell receptor (TCR) repertoire in patients with prolonged disease. Conversely, patients with a CD4 dominant immunophenotype had a lower incidence of prolonged disease and exhibited a deep and highly select COVID-associated TCR repertoire, consistent with effective viral clearance and development of T cell memory. These results highlight the importance of B cells and CD4 T cells in promoting durable SARS-CoV-2 clearance and the significance of coordinated cellular and humoral immunity for long-term disease control.
免疫失调如何影响癌症患者 COVID-19 感染的恢复尚不清楚。我们分析了 103 例既往 COVID-19 感染患者的细胞和体液免疫反应，其中超过 20%的患者病毒清除延迟。病毒清除延迟与核衣壳和刺突蛋白抗体丧失相关，同时功能性 T 细胞反应代偿性增加。外周血样本的高维分析表明，疾病持续时间延长的患者中 CD8 效应 T 细胞分化增加，并且 COVID 特异性 T 细胞受体（TCR）库广泛但融合不佳。相反，具有 CD4 主导免疫表型的患者疾病持续时间延长的发生率较低，并且表现出深度和高度选择的 COVID 相关 TCR 库，这与有效的病毒清除和 T 细胞记忆的发展一致。这些结果强调了 B 细胞和 CD4 T 细胞在促进 SARS-CoV-2 持久清除中的重要性，以及细胞和体液免疫协调对长期疾病控制的意义。
