He Feifan, Zhang Qiuchen, Chen Yunjie, Ge Suli, Xie Yidai, Sun Ruihong, Wu Yuqing, Xu Jian
Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
The Second School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Int J Mol Med. 2025 Aug;56(2). doi: 10.3892/ijmm.2025.5564. Epub 2025 Jun 13.
Cyclin‑dependent kinase (CDK)4/6 inhibitors regulate the cell cycle by binding to CDK4/6, thus exerting an inhibitory effect, and they have a notable impact on tumor immunity. CDK4/6 inhibitors have been demonstrated to modulate the immune microenvironment by affecting immune cells and immune escape phenomena in the tumor microenvironment. T cells, natural killer cells and macrophages are all regulated by CDK4/6 inhibitors, thereby acting on cancer cells. In addition, these inhibitors modulate immune checkpoints, enhancing antitumor immune responses when combined with immune checkpoint inhibitors, such as programmed death‑ligand 1 and programmed death‑1. However, these inhibitors are not without limitations, as they can enhance tumor immune evasion. Therefore, combination therapies to improve efficacy are being investigated, including immunotherapy, targeted therapy, chemotherapy and radiation therapy. In addition, challenges associated with the widespread use of CDK4/6 inhibitors, such as the emergence of tumor resistance, underscore the necessity for further research to enhance the clinical applicability of these inhibitors.
细胞周期蛋白依赖性激酶(CDK)4/6抑制剂通过与CDK4/6结合来调节细胞周期,从而发挥抑制作用,并且它们对肿瘤免疫有显著影响。CDK4/6抑制剂已被证明可通过影响肿瘤微环境中的免疫细胞和免疫逃逸现象来调节免疫微环境。T细胞、自然杀伤细胞和巨噬细胞均受CDK4/6抑制剂调控,进而作用于癌细胞。此外,这些抑制剂可调节免疫检查点,与程序性死亡配体1和程序性死亡1等免疫检查点抑制剂联合使用时可增强抗肿瘤免疫反应。然而,这些抑制剂并非没有局限性,因为它们可增强肿瘤免疫逃逸。因此,正在研究提高疗效的联合疗法,包括免疫疗法、靶向疗法、化疗和放射疗法。此外,与CDK4/6抑制剂广泛使用相关的挑战,如肿瘤耐药性的出现,凸显了进一步研究以提高这些抑制剂临床适用性的必要性。