Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Herston, 4006, Queensland, Australia; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston 4006, Queensland, Australia; School of Medicine, The University of Queensland, Herston 4006, Queensland, Australia.
Unit of Medical Oncology, Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital,Piazza OMS 1, 24100 Bergamo, Italy.
Semin Cancer Biol. 2018 Feb;48:91-103. doi: 10.1016/j.semcancer.2017.04.015. Epub 2017 May 2.
Cancer therapies will increasingly be utilized in combination to treat advanced malignancies so as to increase their long-term efficacy in a greater proportion of patients. In particular, much attention has focused on developing targeted therapies that inhibit the PI3K-AKT-mTOR signaling network which is dysregulated in many cancer types. In addition, there is now a growing appreciation that targeting of these pathways can impact not only on cancer cells, but also host immunity. The clinical success of cancer immunotherapies targeting T-cell immune checkpoint receptors PD-1/PD-L1 has demonstrated the importance of immunoevasion as a hallmark of cancer. In this review, we discuss how PI3K-AKT-mTOR inhibitors target cancer cell biology, attenuate immune cell effector function and modulate the tumor microenvironment. We next discuss how the immunomodulatory potential of these inhibitors can be exploited through rational combinations with immunotherapies and targeted therapies.
癌症疗法将越来越多地联合使用，以治疗晚期恶性肿瘤，从而提高它们在更大比例患者中的长期疗效。特别是，人们非常关注开发靶向治疗方法，以抑制在许多癌症类型中失调的 PI3K-AKT-mTOR 信号网络。此外，现在越来越认识到，靶向这些途径不仅可以影响癌细胞，还可以影响宿主免疫。针对 T 细胞免疫检查点受体 PD-1/PD-L1 的癌症免疫疗法的临床成功证明了免疫逃逸作为癌症标志的重要性。在这篇综述中，我们讨论了 PI3K-AKT-mTOR 抑制剂如何靶向癌细胞生物学、减弱免疫细胞效应功能以及调节肿瘤微环境。接下来，我们讨论了如何通过与免疫疗法和靶向疗法的合理联合来利用这些抑制剂的免疫调节潜力。
