Department of Lymphoma and Hematology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.
Department of Gastroenterology, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.
Hum Vaccin Immunother. 2024 Dec 31;20(1):2408088. doi: 10.1080/21645515.2024.2408088. Epub 2024 Sep 30.
NK/T-cell lymphoma (NKTCL) is a rare type of non-Hodgkin lymphoma (NHL). Although L-asparaginase-based chemotherapy has significantly improved survival in early-stage patients, the prognosis is poor in advanced and relapsed or refractory patients. CD47 is a promising target for cancer immunotherapy. However, the expression of CD47 in NKTCL and the antitumor effect and mechanism of the anti-CD47 monoclonal antibody (mAb) AK117 in NKTCL remain unclear. Firstly, the expression level of CD47 protein in NKTCL cells was detected by immunoblot and flow cytometry. Secondly, in order to validate the role of CD47 downregulation in the proliferation, apoptosis, and cell cycle of NKTCL cells, we used shRNA transfection to knock down CD47 expression. We determined the effect of knocking down CD47 and the novel anti-CD47 antibody AK117 on the phagocytosis of NKYS and YTS cells by M2 macrophages in vitro. Finally, we assessed the ability of AK117 to inhibit tumor growth in an NKTCL xenograft model in which YTS cells were engrafted in SCID mice. The results showed that CD47 is relatively highly expressed in NKTCL cells. CD47 knockdown in NKTCL promoted phagocytosis by M2 macrophages in an in vitro coculture assay. The study also demonstrated that anti-CD47 mAb AK117 promoted phagocytosis of NKTCL cells by M2 macrophages. In addition, in vivo experiments showed that the anti-CD47 mAb AK117 significantly inhibited the growth of subcutaneous xenograft tumors in SCID mice compared to the control antibody IgG. Our results indicate that targeting CD47 monoclonal antibodies is a potential therapeutic strategy for NKTCL.
NK/T 细胞淋巴瘤（NKTCL）是一种罕见的非霍奇金淋巴瘤（NHL）。尽管基于 L-天冬酰胺酶的化疗显著改善了早期患者的生存率，但晚期、复发或难治性患者的预后仍较差。CD47 是癌症免疫治疗的一个有前途的靶点。然而，CD47 在 NKTCL 中的表达以及抗 CD47 单克隆抗体（mAb）AK117 在 NKTCL 中的抗肿瘤作用和机制尚不清楚。首先，通过免疫印迹和流式细胞术检测 NKTCL 细胞中 CD47 蛋白的表达水平。其次，为了验证下调 CD47 对 NKTCL 细胞增殖、凋亡和细胞周期的作用，我们使用 shRNA 转染敲低 CD47 表达。我们确定了敲低 CD47 和新型抗 CD47 抗体 AK117 对 NKYS 和 YTS 细胞被 M2 巨噬细胞吞噬的影响。最后，我们评估了 AK117 在 YTS 细胞植入 SCID 小鼠的 NKTCL 异种移植模型中抑制肿瘤生长的能力。结果表明，CD47 在 NKTCL 细胞中相对高表达。在体外共培养实验中，敲低 NKTCL 中的 CD47 促进了 M2 巨噬细胞的吞噬作用。研究还表明，抗 CD47 mAb AK117 促进了 M2 巨噬细胞对 NKTCL 细胞的吞噬作用。此外，体内实验表明，与对照抗体 IgG 相比，抗 CD47 mAb AK117 显著抑制了 SCID 小鼠皮下异种移植肿瘤的生长。我们的结果表明，靶向 CD47 的单克隆抗体是治疗 NKTCL 的一种潜在治疗策略。
