不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
细胞毒性 CD56^dim CD16⁺ NK 细胞频率降低导致 EBV 阳性经典型霍奇金淋巴瘤抗体依赖性脱颗粒受损
英文原题：Reduced frequency of cytotoxic CD56(dim) CD16(+) NK cells leads to impaired antibody-dependent degranulation in EBV-positive classical Hodgkin lymphoma.
查看英文原题
Reduced frequency of cytotoxic CD56(dim) CD16(+) NK cells leads to impaired antibody-dependent degranulation in EBV-positive classical Hodgkin lymphoma.
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中文摘要
在工业化国家免疫功能正常人群的经典型霍奇金淋巴瘤（cHL）病例中，约 30%–50% 与嗜 B 淋巴细胞的 Epstein-Barr 病毒（EBV）相关。尽管自然杀伤（NK）细胞具有抗病毒和抗肿瘤功能，但 EBV 阳性与 EBV 阴性 cHL 患者的 NK 细胞数量和功能差异几乎无人研究。
本研究前瞻性调查了 36 例诊断时无已知免疫抑制或明显免疫缺陷的 cHL 患者。所有 10 例 EBV 阳性患者及 26 例 EBV 阴性患者中的 25 例均有 EBV 抗体血清阳性；EBV 阳性患者血浆 EBV DNA 水平高于 EBV 阴性患者。研究显示，与 EBV 阴性患者相比，EBV 阳性患者 CD56^dim CD16⁺ NK 细胞亚群比例降低。这一数量缺陷对应于功能受损：与 EBV 阴性患者相比，EBV 阳性患者 CD56^dim NK 细胞对利妥昔单抗包被的 HLA I 类阴性淋巴母细胞样细胞脱颗粒能力下降。研究者还观察到，与健康对照相比，EBV 阳性患者体外扩增 NK 细胞的利妥昔单抗相关脱颗粒及抗体依赖性细胞介导的细胞毒作用有降低趋势。这些发现可能影响针对 EBV 阳性 cHL、以抗体依赖性细胞毒作用为目标的辅助治疗设计。
展开英文摘要原文
Around 30-50% of classical Hodgkin lymphoma (cHL) cases in immunocompetent individuals from industrialized countries are associated with the B-lymphotropic Epstein-Barr virus (EBV). Although natural killer (NK) cells exhibit anti-viral and anti-tumoral functions, virtually nothing is known about quantitative and qualitative differences in NK cells in patients with EBV+ cHL vs. EBV- cHL.
Here, we prospectively investigated 36 cHL patients without known immune suppression or overt immunodeficiency at diagnosis. All 10 EBV+ cHL patients and 25 out 26 EBV- cHL were seropositive for EBV antibodies, and EBV+ cHL patients presented with higher plasma EBV DNA levels compared to EBV- cHL patients.
We show that the CD56 dim CD16 + NK cell subset was decreased in frequency in EBV+ cHL patients compared to EBV- cHL patients. This quantitative deficiency translates into an impaired CD56 dim NK cell mediated degranulation toward rituximab-coated HLA class 1 negative lymphoblastoid cells in EBV+ compared to EBV- cHL patients.
We finally observed a trend to a decrease in the rituximab-associated degranulation and ADCC of in vitro expanded NK cells of EBV+ cHL compared to healthy controls.
Our findings may impact on the design of adjunctive treatment targeting antibody-dependent cellular cytotoxicity in EBV+ cHL.
论文信息
- 作者
- Pánisová E、Lünemann A、Bürgler S、Kotur M、Lazarovici J、Danu A、Kaulfuss M、Mietz J
- 第一作者单位
- Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland.Switzerland
- 通讯作者单位
- Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland. Tarik.Azzi@kispi.uzh.ch.Switzerland
- 期刊
- Cancer immunology, immunotherapy : CII2022 Jan
- 原文标识
- PubMed 33993319 · DOI 10.1007/s00262-021-02956-x
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