靶向NK细胞CLEC12B增强肿瘤免疫治疗，这一成果由中国科学技术大学孙成团队经过不懈努力而取得。2026年3月17日出版的《自然—免疫学》发表了这项成果。

本研究表明，C型凝集素受体CLEC12B作为抑制检查点，限制NK细胞介导的抗肿瘤免疫。肿瘤浸润性NK细胞高表达CLEC12B与肝癌患者临床预后不良相关。该研究团队发现脂蛋白脂肪酶是CLEC12B的功能性配体，可触发抑制NK细胞活化的抑制信号。该课题组开发了一种高亲和力纳米体，作为一种潜在的治疗方法，它可以破坏CLEC12B脂蛋白脂肪酶轴，从而在临床前模型中恢复NK细胞活性并抑制肿瘤进展。

此外，该纳米体与PD-1阻断剂联合使用时具有强大的协同效应。这些发现确立了CLEC12B作为重新武装免疫系统对抗实体恶性肿瘤的一个有希望的治疗靶点。

据悉，自然杀伤（NK）细胞是先天免疫效应细胞，但其细胞毒性可能在免疫抑制的肿瘤微环境中受到损害。确定这种功能障碍背后的分子机制对于癌症免疫治疗的进展至关重要。

附：英文原文

Title: Targeting NK cell CLEC12B enhances cancer immunotherapy

Author: Sun, Peng, Xu, Xiaoyu, Hu, Bian, Zhang, Ke, Khan, Asad, Chen, Huidi, Liu, Hanyang, Khan, Sohail, Tao, Qingping, Nashan, Bjrn, Sun, Cheng

Issue&Volume: 2026-03-17

Abstract: Natural killer (NK) cells are innate immune effectors, but their cytotoxic potential can be compromised within the immunosuppressive tumor microenvironment. Identifying molecular mechanisms that underly this dysfunction is essential for advances in cancer immunotherapy. Here we show that CLEC12B, a C-type lectin receptor, functions as an inhibitory checkpoint that restricts NK cell-mediated antitumor immunity. High expression of CLEC12B by tumor-infiltrating NK cells correlates with poor clinical prognosis in patients with hepatocellular carcinoma. We identify lipoprotein lipase as a functional ligand for CLEC12B, triggering inhibitory signaling that suppresses NK cell activation. We developed a high-affinity nanobody as a potential therapeutic that disrupts the CLEC12B–lipoprotein lipase axis, thereby revitalizing NK cell activity and suppressing tumor progression in preclinical models. Furthermore, this nanobody has potent synergistic efficacy when combined with PD-1 blockade. These findings establish CLEC12B as a promising therapeutic target for rearming the immune system against solid malignancies.

DOI: 10.1038/s41590-026-02471-0

Source: https://www.nature.com/articles/s41590-026-02471-0