Cancer immunotherapy has been rejuvenated by the growing understanding of the immune system's role in tumor activity over the past two decades. During cancer initiation and progression, tumor cells employ various mechanisms that resemble peripheral immune tolerance to evade the antitumor responses of the immune system. Immune checkpoint molecules are the major mechanism of immune resistance that are exploited by tumor cells to inhibit T-cell activation and suppress immune responses. The targeting of immune checkpoint pathways has led to substantial improvements in survival rates in a number of solid cancers. However, a lack of understanding of the heterogeneity of the tumor microenvironment (TME) has resulted in inefficient therapy responses. A greater understanding of the TME is needed to identify patients likely to respond, and those that will have resistance to immune checkpoint inhibitors (ICIs). Advancement in spatial single-cell technologies has allowed deeper insight into the phenotypic and functional diversities of cells in the TME. In this review, we provide an overview of ICI biomarkers and highlight how high-dimensional spatially resolved, single-cell approaches provide deep molecular insights into the TME and allow for the discovery of biomarkers of clinical benefit.

中文翻译：

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免疫检查点抑制剂治疗的组织生物标志物

在过去的二十年中，随着人们对免疫系统在肿瘤活动中的作用的日益了解，癌症免疫疗法重新焕发了活力。在癌症发生和进展过程中，肿瘤细胞利用各种类似于外周免疫耐受的机制来逃避免疫系统的抗肿瘤反应。免疫检查点分子是免疫抵抗的主要机制，肿瘤细胞利用它来抑制 T 细胞活化并抑制免疫反应。免疫检查点通路的靶向已经导致许多实体癌的生存率显着提高。然而，缺乏对肿瘤微环境（TME）异质性的了解导致治疗反应低效。需要对 TME 有更深入的了解，以确定可能有反应的患者以及那些对免疫检查点抑制剂 (ICIs) 产生耐药性的患者。空间单细胞技术的进步使得人们能够更深入地了解 TME 中细胞的表型和功能多样性。在这篇综述中，我们概述了 ICI 生物标志物，并强调了高维空间分辨的单细胞方法如何提供对 TME 的深入分子洞察，并允许发现具有临床益处的生物标志物。