Department of Pathology, Wake Forest University School of Medicine, Winston Salem, NC; Department of Laboratory Medicine, Cleveland Clinic, Cleveland OH.
Carolinas Pathology Group, Charlotte, NC.
Clin Lymphoma Myeloma Leuk. 2024 Nov;24(11):e808-e818. doi: 10.1016/j.clml.2024.06.013. Epub 2024 Jul 8.
Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentiation. This study aimed to investigate the CD6 expression in these malignancies and explore the potential of targeting CD6 in these diseases.
We conducted a retrospective study with totally 41 cases to investigate the expression of CD6 by immunohistochemistry, including aggressive NK-cell leukemia/lymphoma (ANKLL: N = 10) and extranodal NK/T-cell lymphoma (ENKTL: N = 31). A novel ANKLL model was applied for proof-of-concept functional studies of a CD6 antibody-drug-conjugate (CD6-ADC) both in vitro and in animal trial.
CD6 was expressed in 68.3% (28/41) of cases (70% (7/10) of ANKLL and 67.7% (21/31) of ENKTL). The median overall survival (OS) for ANKLL and ENTKL cases was 1 and 12 months, respectively, with no significant difference in OS based on CD6 expression (p > 0.05, Kaplan-Meier with log-rank test). In vitro exposure of the CCANKL cell line, derived from an ANKL patient, to an anti-CD6ADC resulted in dose dependent induction of apoptosis. Furthermore, CCANKL engraftment in NSG mice could be blocked by treatment with the anti-CD6 ADC.
To date, this is the first report to explore the expression of CD6 in ANKLL and ENKTL and confirms its expression in the majority of cases. The in vitro and in vivo data support further investigation of CD6 as a potential therapeutic target in these aggressive NK/T-cell malignancies.
侵袭性 NK/T 细胞肿瘤是一种罕见的血液系统恶性肿瘤，其特征为 NK 或 NK 样 T（NK/T）细胞异常增殖。CD6 是一种参与淋巴细胞激活和分化的跨膜信号转导受体。本研究旨在探讨这些恶性肿瘤中 CD6 的表达，并探索针对这些疾病中 CD6 的潜在治疗靶点。
我们进行了一项回顾性研究，共纳入 41 例侵袭性 NK/T 细胞肿瘤患者，包括侵袭性 NK 细胞白血病/淋巴瘤（ANKLL：N=10）和结外 NK/T 细胞淋巴瘤（ENKTL：N=31）。我们应用一种新型 ANKLL 模型，进行 CD6 抗体药物偶联物（CD6-ADC）的体外和动物试验功能研究。
41 例病例中，CD6 表达阳性率为 68.3%（28/41）（ANKLL 中为 70%（7/10），ENKTL 中为 67.7%（21/31））。ANKLL 和 ENTKL 病例的中位总生存期（OS）分别为 1 个月和 12 个月，根据 CD6 表达情况，OS 无显著差异（p＞0.05，Kaplan-Meier 对数秩检验）。体外实验中，用抗 CD6 ADC 处理源自 ANKL 患者的 CCANKL 细胞系，可导致凋亡呈剂量依赖性诱导。此外，用抗 CD6 ADC 治疗可阻断 CCANKL 细胞在 NSG 小鼠中的植入。
迄今为止，这是首次探索 CD6 在 ANKLL 和 ENKTL 中的表达，并证实其在大多数病例中表达。体外和体内数据支持进一步研究 CD6 作为这些侵袭性 NK/T 细胞恶性肿瘤的潜在治疗靶点。
