The successes with immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR)-T-cell therapy in treating multiple cancer types have established immunotherapy as a powerful curative option for patients with advanced cancers. Unfortunately, many patients do not derive benefit or long-term responses, highlighting a pressing need to perform complete investigation of the underlying mechanisms and the immunotherapy-induced tumor regression or rejection. In recent years, a large number of single-cell technologies have leveraged advances in characterizing immune system, profiling tumor microenvironment, and identifying cellular heterogeneity, which establish the foundations for lifting the veil on the comprehensive crosstalk between cancer and immune system during immunotherapies. In this review, we introduce the applications of the most widely used single-cell technologies in furthering our understanding of immunotherapies in terms of underlying mechanisms and their association with therapeutic outcomes. We also discuss how single-cell analyses help to deliver new insights into biomarker discovery to predict patient response rate, monitor acquired resistance, and support prophylactic strategy development for toxicity management. Finally, we provide an overview of applying cutting-edge single-cell spatial-omics to point out the heterogeneity of tumor–immune interactions at higher level that can ultimately guide to the rational design of next-generation immunotherapies.
免疫检查点抑制剂（immune checkpoint blockade）和嵌合抗原受体T细胞（Chimeric antigen receptor-T cell，CAR-T）在多种癌症治疗中取得的成功使得免疫疗法成为恶性肿瘤的潜在有力克星。但不幸的是，仍然有许多病人无法从这些新疗法中获益或者疗效持续时间短暂。因此，全面深入的剖析疗效背后的分子机制、明确与治疗相关的肿瘤消退或抗药原因尤为迫切。近几年，众多单细胞分析技术在表征免疫系统、研究肿瘤微环境、解读细胞间异质性等应用中发挥着日益重要的作用、取得了一系列突破性进展，为进一步了解免疫治疗过程中癌细胞与免疫细胞的交互作用奠定了基础。本文综述介绍了当前应用最广泛的单细胞技术在解读免疫疗法的作用机制及其与临床治疗效果的关联中取得的重要成果，讨论了这些技术如何通过发现生物标志物来预测疗效、监测复发及针对临床相关副反应开发预防性措施。最后，本文概述并展望了当前最先进的空间组学技术在组织层面以更高准确度明晰肿瘤-免疫相互作用、助力下一代免疫疗法开发的前景。





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