Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
The Parker Institute for Cancer Immunotherapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2022 Sep 15;28(18):3917-3928. doi: 10.1158/1078-0432.CCR-21-1804.
Basic science breakthroughs in T-cell biology and immune-tumor cell interactions ushered in a new era of cancer immunotherapy. Twenty years ago, cancer immunoediting was proposed as a framework to understand the dynamic process by which the immune system can both control and shape cancer and in its most complex form occurs through three phases termed elimination, equilibrium, and escape. During cancer progression through these phases, tumors undergo immunoediting, rendering them less immunogenic and more capable of establishing an immunosuppressive microenvironment. Therefore, cancer immunoediting integrates the complex immune-tumor cell interactions occurring in the tumor microenvironment and sculpts immunogenicity beyond shaping antigenicity. However, with the success of cancer immunotherapy resulting in durable clinical responses in the last decade and subsequent emergence of immuno-oncology as a clinical subspecialty, the phrase "cancer immunoediting" has recently, at times, been inappropriately restricted to describing neoantigen loss by immunoselection. This focus has obscured other mechanisms by which cancer immunoediting modifies tumor immunogenicity. Although establishment of the concept of cancer immunoediting and definitive experimental evidence supporting its existence was initially obtained from preclinical models in the absence of immunotherapy, cancer immunoediting is a continual process that also occurs during immunotherapy in human patients with cancer. Herein, we discuss the known mechanisms of cancer immunoediting obtained from preclinical and clinical data with an emphasis on how a greater understanding of cancer immunoediting may provide insights into immunotherapy resistance and how this resistance can be overcome.
基础科学在 T 细胞生物学和免疫-肿瘤细胞相互作用方面的突破开创了癌症免疫治疗的新时代。二十年前,癌症免疫编辑被提出作为一个框架来理解免疫系统控制和塑造癌症的动态过程,在其最复杂的形式中,通过三个阶段来实现,即消除、平衡和逃逸。在肿瘤通过这些阶段进展的过程中,肿瘤经历免疫编辑,使其免疫原性降低,更有能力建立免疫抑制性微环境。因此,癌症免疫编辑整合了肿瘤微环境中发生的复杂免疫-肿瘤细胞相互作用,并在塑造抗原性之外塑造免疫原性。然而,随着癌症免疫治疗在过去十年中取得了持久的临床反应,并随后出现了肿瘤免疫学作为一个临床亚专科,“癌症免疫编辑”这个短语最近有时被不恰当地限制在描述免疫选择导致的新抗原丢失。这种关注掩盖了癌症免疫编辑改变肿瘤免疫原性的其他机制。尽管癌症免疫编辑概念的建立和支持其存在的明确实验证据最初是从缺乏免疫治疗的临床前模型中获得的,但癌症免疫编辑是一个持续的过程,也发生在人类癌症患者的免疫治疗过程中。在此,我们讨论了从临床前和临床数据中获得的癌症免疫编辑的已知机制,并强调了更深入地了解癌症免疫编辑如何为免疫治疗耐药性提供见解,以及如何克服这种耐药性。
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