Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cancer Cell. 2018 Apr 9;33(4):581-598. doi: 10.1016/j.ccell.2018.03.005.
Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from "self," generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization.
检查点阻断已正式表明，重新激活抗肿瘤免疫反应可以使肿瘤消退。然而，这种情况仅发生在一部分患者中。因此，将这些疗法纳入更有效的联合治疗是合乎逻辑的下一步。在这里，我们回顾了免疫检查点的功能作用和检查点阻断临床活性的分子决定因素。与“自身”有很大不同的、浸润有限数量 T 细胞的肿瘤通常对检查点阻断有反应。因此，我们提出减少肿瘤负担和提高肿瘤免疫原性是改善免疫治疗的关键因素。最后，我们概述了选择适当的免疫治疗联合治疗伙伴的标准，并强调了活性生物标志物对于及时优化治疗的重要性。
