Preexisting and Post-COVID-19 Immune Responses to SARS-CoV-2 in Patients with Cancer
Preexisting and Post-COVID-19 Immune Responses to SARS-CoV-2 in Patients with Cancer
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DOI：
10.1158/2159-8290.cd-21-0191
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发表时间：
2021-08-01
期刊：
影响因子：
28.2
通讯作者：
Walz, Juliane S.
中科院分区：
文献类型：
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作者：
Bilich, Tatjana;Roerden, Malte;Walz, Juliane S.
癌症患者，特别是患有血液系统恶性肿瘤的患者，在感染 COVID-19 后患危重疾病的风险增加。我们在这里评估了未暴露的和感染 SARS-CoV-2 的癌症患者的抗体以及 CD4(+) 和 CD8(+) T 细胞反应，以表征 SARS-CoV-2 免疫并确定有助于 COVID-19 结果的免疫参数。与实体瘤患者和健康志愿者相比，未暴露的血液恶性肿瘤患者先前存在的 SARS-CoV-2 交叉反应性 CD4(+) T 细胞反应的发生率降低，并且出现 T 细胞耗竭的迹象。尽管 SARS-CoV-2 抗体反应在 COVID-19 患者、癌症患者和健康志愿者之间没有差异，但癌症患者中 SARS-CoV-2 T 细胞反应的强度、扩展性和多样性显着降低，而后者与 COVID-19 的严重病程相关。这表明 SARS-CoV-2 T 细胞免疫受损是癌症患者 COVID-19 预后不佳的潜在决定因素。 意义：首次对癌症患者 SARS-CoV-2 免疫反应进行全面分析，报告了 SARS-CoV-2 T 细胞反应受损对了解病理生理学和预测 COVID-19 严重程度的潜在影响，从而可能为这一弱势患者群体开发治疗措施和疫苗。
Patients with cancer, in particular patients with hematologic malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4(+) and CD8(+) T-cell responses in unexposed and SARS-CoV-2-infected patients with cancer to characterize SARS-CoV-2 immunity and to identify immunologic parameters contributing to COVID-19 outcome. Unexposed patients with hematologic malignancies presented with reduced prevalence of preexisting SARS-CoV-2 cross-reactive CD4(+) T-cell responses and signs of T-cell exhaustion compared with patients with solid tumors and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between patients with COVID-19 and cancer and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T-cell responses were profoundly reduced in patients with cancer, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T-cell immunity as a potential determinant for dismal outcome of COVID-19 in patients with cancer.SIGNIFICANCE: This first comprehensive analysis of SARS-CoV-2 immune responses in patients with cancer reports on the potential implications of impaired SARS-CoV-2 T-cell responses for understanding pathophysiology and predicting severity of COVID-19, which in turn might allow for the development of therapeutic measures and vaccines for this vulnerable patient population.