PDF(Pubmed)
Abstract：
Anticancer immunotherapies, such as immune checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T cells, have improved outcomes for patients with a variety of malignancies. However, most patients either do not initially respond or do not exhibit durable responses due to primary or adaptive/acquired immune resistance mechanisms of the tumor microenvironment. These suppressive programs are myriad, different between patients with ostensibly the same cancer type, and can harness multiple cell types to reinforce their stability. Consequently, the overall benefit of monotherapies remains limited. Cutting-edge technologies now allow for extensive tumor profiling, which can be used to define tumor cell intrinsic and extrinsic pathways of primary and/or acquired immune resistance, herein referred to as features or feature sets of immune resistance to current therapies. We propose that cancers can be characterized by immune resistance archetypes, comprised of five feature sets encompassing known immune resistance mechanisms. Archetypes of resistance may inform new therapeutic strategies that concurrently address multiple cell axes and/or suppressive mechanisms, and clinicians may consequently be able to prioritize targeted therapy combinations for individual patients to improve overall efficacy and outcomes.
摘要：
抗癌免疫疗法，如免疫检查点抑制剂，双特异性抗体，和嵌合抗原受体T细胞，改善了各种恶性肿瘤患者的预后。然而,由于肿瘤微环境的原发性或适应性/获得性免疫抵抗机制，大多数患者最初没有反应或没有表现出持久的反应。这些抑制程序是无数的，表面上相同癌症类型的患者不同，并且可以利用多种细胞类型来增强其稳定性。因此,单一疗法的总体获益仍然有限.尖端技术现在允许广泛的肿瘤分析，可用于定义肿瘤细胞的原发性和/或获得性免疫抗性的内在和外在途径，本文中称为对当前疗法的免疫抗性的特征或特征集。我们建议癌症可以通过免疫抗性原型来表征，由包含已知免疫抵抗机制的五个特征集组成。抗性的原型可以提供新的治疗策略，同时解决多个细胞轴和/或抑制机制。因此,临床医生可能能够优先考虑针对个体患者的靶向治疗组合,以改善总体疗效和结局.
