CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study.
Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study.
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迄今为止，这是首个探讨 CD6 在 ANKLL 和 ENKTL 中表达的研究，并证实其在大多数病例中均有表达。体外和体内数据支持进一步研究 CD6 作为这些侵袭性 NK/T 细胞恶性肿瘤潜在治疗靶点的可能性。
侵袭性NK/T细胞肿瘤是一种罕见的血液系统恶性肿瘤，其特征在于NK或NK样T（NK/T）细胞的异常增殖。CD6是一种参与淋巴细胞活化和分化的跨膜信号转导受体。本研究旨在调查这些恶性肿瘤中CD6的表达，并探索靶向CD6在这些疾病中的潜力。
我们进行了一项回顾性研究，共41例，通过免疫组化检测CD6的表达，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）。在体外和动物实验中，应用一种新的ANKLL模型对CD6抗体-药物偶联物（CD6-ADC）进行了概念验证性功能研究。
CD6在68.3%（28/41）的病例中表达（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，基于CD6表达的OS无显著差异（p > 0.05，Kaplan-Meier法及log-rank检验）。将来源于ANKL患者的CCANKL细胞系在体外暴露于抗CD6 ADC后，可导致剂量依赖性的凋亡诱导。此外，NSG小鼠中CCANKL的植入可被抗CD6 ADC治疗所阻断。
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.
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