免疫系统在控制慢性粒细胞白血病（CML）中发挥着关键作用。 CD8 T 细胞耗竭会导致 T 细胞介导的免疫效果降低，从而导致疾病进展。本研究旨在弄清楚抑制分子 TIM-3/PD-1 的联合阻断是否会影响 CML 中 CD8 T 细胞的耗竭。通过移植表达 BCR-ABL 的逆转录病毒载体转导的骨髓细胞建立 CML 小鼠模型。使用相应的分子抗体阻断 PD-1 和 TIM-3 信号传导。进行流式细胞术分析以检测细胞表面分子和细胞内细胞因子。采用ELISA来测量培养基中的细胞因子浓度。结果表明，TIM-3 和 PD-1 在 CML 小鼠耗竭的 CD8 T 细胞上共表达。联合阻断 PD-1/TIM3 可协同延缓小鼠 CML 进展。此外，离体实验表明，它们的共同阻断促进了从 CML 小鼠中分离的 CD8 T 细胞的增殖和细胞因子分泌。总之，阻断 TIM-3 和 PD-1 可改善 CML 中耗尽的 CD8 T 细胞功能。© 2024。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下子公司）的独家许可。

The immune system plays a pivotal role in controlling chronic myeloid leukemia (CML). CD8+ T cell exhaustion results in reduced effectiveness of T cell-mediated immunity, thereby contributing to disease progression. This study intends to figure out whether the combined blockade of inhibitory molecules TIM-3/PD-1 can affect CD8+ T cell exhaustion in CML. A CML mouse model was established via transplantation of bone marrow cells transduced with BCR-ABL-expressing retrovirus vectors. PD-1 and TIM-3 signaling were blocked using corresponding molecular antibodies. Flow cytometry analysis was conducted to detect cell surface molecules and intracellular cytokines. ELISA was employed for measuring cytokine concentrations in the culture medium. The results showed that TIM-3 and PD-1 were coexpressed on exhausted CD8+ T cells from CML mice. Combined blockade of PD-1/TIM3 synergistically delayed CML progression in mice. Moreover, ex vivo experiments showed that their co-blockade promoted the proliferation and cytokine secretion of CD8+ T cells isolated from CML mice. In conclusion, blocking TIM-3 and PD-1 improves exhausted CD8+ T cell function in CML.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.