Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), has recently been approved for the treatment of hormone receptor-positive breast cancer. In this study, we use murine syngeneic tumor models and in vitro assays to investigate the impact of abemaciclib on T cells, the tumor immune microenvironment and the ability to combine with anti-PD-L1 blockade. Abemaciclib monotherapy resulted in tumor growth delay that was associated with an increased T cell inflammatory signature in tumors. Combination with anti-PD-L1 therapy led to complete tumor regressions and immunological memory, accompanied by enhanced antigen presentation, a T cell inflamed phenotype, and enhanced cell cycle control. In vitro, treatment with abemaciclib resulted in increased activation of human T cells and upregulated expression of antigen presentation genes in MCF-7 breast cancer cells. These data collectively support the clinical investigation of the combination of abemaciclib with agents such as anti-PD-L1 that modulate T cell anti-tumor immunity.

中文翻译：

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CDK4 / 6抑制剂Abemaciclib诱导T细胞发炎的肿瘤微环境，并增强PD-L1检查点封锁的功效。

Abemaciclib是细胞周期蛋白依赖性激酶4和6（CDK4 / 6）的抑制剂，最近被批准用于治疗激素受体阳性的乳腺癌。在这项研究中，我们使用鼠类同系肿瘤模型和体外测定法来研究abemaciclib对T细胞的影响，肿瘤免疫微环境以及与抗PD-L1阻断剂结合的能力。Abemaciclib单药治疗导致肿瘤生长延迟，这与肿瘤中T细胞炎症信号的增加有关。与抗PD-L1治疗相结合可导致肿瘤的完全消退和免疫记忆，并伴随着增强的抗原呈递，T细胞发炎的表型和增强的细胞周期控制。体外，用abemaciclib进行的治疗导致MCF-7乳腺癌细胞中人类T细胞的活化增加以及抗原呈递基因的表达上调。这些数据共同支持abemaciclib与调节T细胞抗肿瘤免疫力的药物如抗PD-L1组合的临床研究。