Maleki Vareki Saman, Garrigós Carmen, Duran Ignacio
Cancer Research Laboratory Program, Lawson Health Research Institute, London, Ontario, Canada.
Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Crit Rev Oncol Hematol. 2017 Aug;116:116-124. doi: 10.1016/j.critrevonc.2017.06.001. Epub 2017 Jun 9.
Immunotherapy is a promising treatment strategy for cancer that has recently shown unprecedented survival benefits in selected patients. A number of immunomodulatory agents that target immune system checkpoints such as the cytotoxic T-lymphocyte antigen 4 (CTLA-4), the programmed death-1 (PD-1) or its ligand (PD-L1), have received regulatory approval for the treatment of multiple cancers including malignant melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic head and neck squamous cell carcinoma. Nevertheless, a substantial proportion of patients treated with checkpoint inhibitors have little or no benefit while these treatments are costly and might have associated toxicities. Hence, the establishment of valid predictors of treatment response has become a priority. This review summarizes the current evidence around biomarkers of response to PD-1/PD-L1 inhibition, considering features related to the tumor and to the host immune system.
免疫疗法是一种很有前景的癌症治疗策略,最近已在部分患者中显示出前所未有的生存获益。一些靶向免疫系统检查点的免疫调节药物,如细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性死亡蛋白1(PD-1)或其配体(PD-L1),已获得监管部门批准,用于治疗多种癌症,包括恶性黑色素瘤、非小细胞肺癌、肾细胞癌、经典型霍奇金淋巴瘤以及复发或转移性头颈部鳞状细胞癌。然而,相当一部分接受检查点抑制剂治疗的患者获益甚微或毫无益处,而且这些治疗费用高昂,还可能伴有毒性。因此,建立有效的治疗反应预测指标已成为当务之急。本综述总结了目前关于PD-1/PD-L1抑制反应生物标志物的证据,同时考虑了与肿瘤和宿主免疫系统相关的特征。