CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Dual blockades of TIM-3 and PD-1 effectively prevent hyper-progression and enhance the efficacy of anti-PD-1 therapy in high-grade serous ovarian cancer.
Dual blockades of TIM-3 and PD-1 effectively prevent hyper-progression and enhance the efficacy of anti-PD-1 therapy in high-grade serous ovarian cancer.
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程序性细胞死亡1（PD-1）在高grade浆液性卵巢癌（HGSOC）中疗效有限，平均缓解率为10%至15%。此外，超进展疾病（HPD）主要发生在免疫检查点阻断（ICB）治疗下，是ICB治疗的一种潜在有害副作用，会加速HGSOC患者的疾病进展。
我们的研究旨在在临床前环境中确定提高抗PD-1治疗对HGSOC疗效的方法。在抗PD-1治疗后，ID8 VEGF荷瘤小鼠中观察到CD8+TIL（肿瘤浸润淋巴细胞）（TILs）和肿瘤浸润树突状细胞（TIDCs）中TIM-3的显著上调以及HPD现象。TIM-3和PD-1联合阻断在临床前模型中预防了HPD的发生并延长了其生存期。
同时，TIM-3和PD-1联合阻断有效增强了ID8 VEGF荷瘤小鼠CD8+ TILs和TIDCs的功能和增殖。值得注意的是，TIM-3和PD-1抑制剂有效增强了HGSOC患者CD8+ TILs和CD11c+髓系细胞的抗肿瘤免疫。
我们的研究揭示了TIM-3抑制在预防HPD发生和增强HGSOC抗PD-1治疗疗效中的重要意义。
The programmed cell death 1 (PD-1), exhibits limited efficacy in high-grade serous ovarian cancer (HGSOC), with an average response rate of 10 to 15%.
Furthermore, hyper-progression disease (HPD), which mostly occurs under immune checkpoint blockade (ICB) therapy, is a potentially deleterious side effect of ICB therapy that accelerates disease progression in HGSOC patients.
Our study aims to identify the approach to improve the efficacy of anti-PD-1 treatment on HGSOC in preclinical settings. The prominent TIM-3 upregulation in CD8 + tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating dendritic cells (TIDCs) and the phenomenon of HPD were observed in ID8 VEGF -bearing mice after anti-PD-1 treatment.
TIM-3 and PD-1 co-blockades prevented the occurrence of HPD in pre-clinical models and prolonged their survival. Meanwhile, TIM-3 and PD-1 co-blockades effectively enhanced the function and proliferation of CD8 + TILs and TIDCs from ID8 VEGF -bearing mice.
Notably, TIM-3 and PD-1 inhibitors effectively enhanced the anti-tumor immunity of CD8 + TILs and CD11c + myeloid cells from HGSOC patients.
Our study uncovers the significance of TIM-3 inhibition in preventing the occurrence of HPD and enhancing the efficacy of anti-PD-1 therapy in HGSOC.
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