肿瘤细胞治疗研究
英文原题：Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients.
我们的结果表明，疫苗应答者显示出细胞毒性CD4+ T细胞和表达FAS+/TIM3+的成熟CD38+ NK细胞的显著过度代表，并具有强烈的细胞因子反应性，如I型干扰素、IL-12和TNF-α介导的信号传导。
多发性骨髓瘤（MM）患者常规接种 mRNA 疫苗以降低 COVID-19 相关死亡率。然而，疾病及治疗相关的免疫细胞改变和细胞因子反应性是否导致了观察到的异质性疫苗接种反应，目前尚不清楚。因此，我们采用全转录组和表面蛋白质组单细胞分析，结合功能性血清学和 T 细胞验证，对 58 例 MM 患者在 SARS-CoV-2 疫苗接种期间及突破性感染（BTI）后的外周血单个核细胞进行了分析。我们的结果表明，疫苗应答者中细胞毒性 CD4+ T 细胞和表达 FAS+/TIM3+ 的成熟 CD38+ NK 细胞显著过表达，并具有强烈的细胞因子反应性，如 I 型干扰素、IL-12 和 TNF-α 介导的信号传导。发生 BTI 的 MM 患者产生了强烈的血清学和细胞反应，并表现出与疫苗应答者相似的细胞因子反应性免疫细胞模式。本研究可拓展我们对免疫接种反应相关分子和细胞模式的理解，并可能有助于为免疫功能低下患者设计改进的疫苗接种策略。
Patients with multiple myeloma (MM) routinely receive mRNA-based vaccines to reduce COVID-19-related mortality. However, whether disease- and therapy-related alterations in immune cells and cytokine-responsiveness contribute to the observed heterogeneous vaccination responses is unclear. Thus, we analyzed peripheral blood mononuclear cells from patients with MM during and after SARS-CoV-2 vaccination and breakthrough infection (BTI) using combined whole-transcriptome and surface proteome single-cell profiling with functional serological and T-cell validation in 58 MM patients. Our results demonstrate that vaccine-responders showed a significant overrepresentation of cytotoxic CD4 + T- and mature CD38 + NK-cells expressing FAS + /TIM3 + with a robust cytokine-responsiveness, such as type-I-interferon-, IL-12- and TNF-α-mediated signaling. Patients with MM experiencing BTI developed strong serological and cellular responses and exhibited similar cytokine-responsive immune cell patterns as vaccine-responders. This study can expand our understanding of molecular and cellular patterns associated with immunization responses and may benefit the design of improved vaccination strategies in immunocompromised patients.
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