Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Thoracic Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Cell Immunol. 2021 Apr;362:104301. doi: 10.1016/j.cellimm.2021.104301. Epub 2021 Feb 4.
Immuno checkpoint blockade (ICB) targeting the PD-1/PD-L1 axis is the main breakthrough for the treatment of several cancers. Nevertheless, not all patients benefit from this treatment and clinical response not always correlates with PD-L1 expression by tumor cells. The tumor microenvironment, including myeloid derived suppressor cells (MDSCs), can influence therapeutic resistance to ICB. MDSCs also express PD-L1, which contributes to their suppressive activity. Moreover, anticancer therapies including chemotherapy, radiotherapy, hormone- and targeted- therapies can modulate MDSCs recruitment, activity and PD-L1 expression. Such effects can be induced also by innovative anticancer treatments targeting metabolism and lifestyle. The outcome on cancer progression can be either positive or negative, depending on tumor type, treatment schedule and possible combination with ICB. Further studies are needed to better understand the effects of cancer therapies on the PD-1/PD-L1 axis, to identify patients that could benefit from combinatorial regimens including ICB or that rather should avoid it.
免疫检查点阻断（ICB）针对 PD-1/PD-L1 轴是治疗多种癌症的主要突破。然而，并非所有患者都从这种治疗中受益，并且临床反应并不总是与肿瘤细胞的 PD-L1 表达相关。肿瘤微环境，包括髓源抑制细胞（MDSCs），可以影响对 ICB 的治疗抵抗。MDSCs 也表达 PD-L1，这有助于其抑制活性。此外，包括化疗、放疗、激素和靶向治疗在内的抗癌疗法可以调节 MDSCs 的募集、活性和 PD-L1 表达。针对代谢和生活方式的创新抗癌疗法也可以诱导这种作用。癌症进展的结果可能是阳性的，也可能是阴性的，这取决于肿瘤类型、治疗方案以及与 ICB 的可能联合。需要进一步的研究来更好地了解癌症疗法对 PD-1/PD-L1 轴的影响，以确定哪些患者可能从包括 ICB 的联合治疗方案中受益，或者哪些患者应避免使用 ICB。
