Research Unit, Hospital Costa del Sol. Autovía A7, km 187. Marbella, 29603 Málaga, Spain.
Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), 28029 Madrid, Spain.
Int J Mol Sci. 2019 May 9;20(9):2296. doi: 10.3390/ijms20092296.
The interaction between programmed cell death protein (PD-1) and its ligand (PD-L1) is one of the main pathways used by some tumors to escape the immune response. In recent years, immunotherapies based on the use of antibodies against PD-1/PD-L1 have been postulated as a great promise for cancer treatment, increasing total survival compared to standard therapy in different tumors. Despite the hopefulness of these results, a significant percentage of patients do not respond to such therapy or will end up evolving toward a progressive disease. Besides their role in PD-L1 expression, altered protein kinases in tumor cells can limit the effectiveness of PD-1/PD-L1 blocking therapies at different levels. In this review, we describe the role of kinases that appear most frequently altered in tumor cells and that can be an impediment for the success of immunotherapies as well as the potential utility of protein kinase inhibitors to enhance the response to such treatments.
程序性死亡蛋白 1（PD-1）与其配体（PD-L1）的相互作用是一些肿瘤逃避免疫反应的主要途径之一。近年来，基于使用抗 PD-1/PD-L1 抗体的免疫疗法被认为是癌症治疗的一大希望，与不同肿瘤的标准疗法相比，总生存率有所提高。尽管这些结果充满希望，但仍有相当一部分患者对这种治疗没有反应，或者最终会发展为进行性疾病。除了在 PD-L1 表达中的作用外，肿瘤细胞中改变的蛋白激酶可以在不同水平上限制 PD-1/PD-L1 阻断疗法的有效性。在这篇综述中，我们描述了在肿瘤细胞中最常发生改变的激酶的作用，这些激酶可能会阻碍免疫疗法的成功，以及蛋白激酶抑制剂增强对这些治疗反应的潜在用途。
