免疫检查点抑制剂（ICIs）的使用持续改变非小细胞肺癌（NSCLC）的治疗格局，这些药物正在评估疾病的每个阶段。与这些进展相比，有关可靠的预测性生物标志物在治疗效果上能向临床医生提供信息的进展却很少。所有目前用于预测结果的生物标志物，包括PD-L1、肿瘤突变负荷或复杂免疫基因表达签名，都需要获得肿瘤组织。除取样程序的侵入性外，肿瘤组织活检的其他缺点还包括无法捕获肿瘤的完整空间异质性和进行长期治疗跟踪的困难。一个概念出现了，在离肿瘤远处发展的全身免疫事件反映了免疫治疗的局部响应或耐药性。对外周血免疫细胞亚群进行全面分析可以解读这种癌症的“宏环境”的重要性，这一点在几个尖端的临床前研究中已经得到证实，并得到免疫检查点抑制剂治疗患者有趣数据的支持。在这篇综述中，我们将提供基于血液免疫细胞为基础的生物学理论，用以指导免疫治疗适应于NSCLC患者的治疗决策。最后，我们将描述一些新技术，以促进发现更多可能成为预测性生物标志物的免疫细胞亚群，并就将这种分析方法带入近期常规临床护理中的途径和尚需解决的挑战进行讨论。© 作者（或其雇主）2023年的著作。在CC BY-NC下许可再使用。不允许商业再使用。由BMJ出版。

The use of immune checkpoint inhibitors (ICIs) continues to transform the therapeutic landscape of non-small cell lung cancer (NSCLC), with these drugs now being evaluated at every stage of the disease. In contrast to these advances, little progress has been made with respect to reliable predictive biomarkers that can inform clinicians on therapeutic efficacy. All current biomarkers for outcome prediction, including PD-L1, tumor mutational burden or complex immune gene expression signatures, require access to tumor tissue. Besides the invasive nature of the sampling procedure, other disadvantages of tumor tissue biopsies are the inability to capture the complete spatial heterogeneity of the tumor and the difficulty to perform longitudinal follow-up on treatment. A concept emerges in which systemic immune events developing at a distance from the tumor reflect local response or resistance to immunotherapy. The importance of this cancer 'macroenvironment', which can be deciphered by comprehensive analysis of peripheral blood immune cell subsets, has been demonstrated in several cutting-edge preclinical reports, and is corroborated by intriguing data emerging from ICI-treated patients. In this review, we will provide the biological rationale underlying the potential of blood immune cell-based biomarkers in guiding treatment decision in immunotherapy-eligible NSCLC patients. Finally, we will describe new techniques that will facilitate the discovery of more immune cell subpopulations with potential to become predictive biomarkers, and reflect on ways and the remaining challenges to bring this type of analysis to the routine clinical care in the near future.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.