肿瘤细胞治疗研究
英文原题：Selective targeting of IL2Rβγ combined with radiotherapy triggers CD8- and NK-mediated immunity, abrogating metastasis in HNSCC.
Selective targeting of IL2Rβγ combined with radiotherapy triggers CD8- and NK-mediated immunity, abrogating metastasis in HNSCC.
这些数据表明，PD1-L2v 在 HNSCC 中诱导了持久的全身性肿瘤控制。
癌症免疫疗法在头颈部鳞状细胞癌（HNSCC）中的临床成功有限。白细胞介素-2（IL-2）可调节淋巴细胞的存活和功能，是新型免疫疗法的一个有吸引力的靶点，但受限于表达高亲和力 IL-2Rα 的调节性 T 细胞（Tregs）的存在。双特异性免疫细胞因子 PD1-IL2v 优先通过 PD-1 表达细胞上的 IL-2Rβγ 传递 IL-2 信号。选择性靶向中等亲和力的 IL-2Rβγ 可用于诱导效应 T 细胞和自然杀伤（NK）细胞的抗肿瘤免疫应答，同时限制 IL-2Rα 激活对 Tregs 的负向调控。放射治疗（RT）联合 PD1-IL2v 可改善局部肿瘤控制和生存，并在原位 HNSCC 肿瘤模型中控制转移扩散。PD1-IL2v 驱动循环和肿瘤浸润性细胞毒性 T 细胞及 NK 细胞的全身性激活和扩增，同时限制 Treg 介导的免疫抑制。这些数据表明，PD1-L2v 在 HNSCC 中诱导持久的全身性肿瘤控制。
The implementation of cancer immunotherapies has seen limited clinical success in head and neck squamous cell carcinoma (HNSCC). Interleukin-2 (IL-2), which modulates the survival and functionality of lymphocytes, is an attractive target for new immunotherapies but one that is limited by presence of regulatory T cells (Tregs) expressing the high-affinity IL-2Rα. The bispecific immunocytokine PD1-IL2v preferentially delivers IL-2 signaling through IL-2Rβγ on PD-1-expressing cells. Selectively targeting the intermediate-affinity IL-2Rβγ can be leveraged to induce anti-tumor immune responses in effector T cells and natural killer (NK) cells while limiting the negative regulation of IL-2Rα activation on Tregs. Using radiation therapy (RT) in combination with PD1-IL2v improves local tumor control and survival, and controls metastatic spread in orthotopic HNSCC tumor models. PD1-IL2v drives systemic activation and expansion of circulating and tumor-infiltrating cytotoxic T cells and NK cells while limiting Treg-mediated immunosuppression. These data show that PD1-L2v induces durable systemic tumor control in HNSCC.
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