VIB UGent Center for Medical Biotechnology, Ghent, Belgium.
Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
J Immunother Cancer. 2023 Aug;11(8). doi: 10.1136/jitc-2023-007023.
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.
免疫检查点抑制剂（ICIs）的应用不断改变着非小细胞肺癌（NSCLC）的治疗格局，这些药物现在正在疾病的各个阶段进行评估。与这些进展形成对比的是，在能够为临床医生提供治疗效果信息的可靠预测性生物标志物方面，几乎没有取得任何进展。目前所有用于预后预测的生物标志物，包括 PD-L1、肿瘤突变负担或复杂的免疫基因表达特征，都需要获取肿瘤组织。除了采样过程的侵入性之外，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，以及难以对治疗进行纵向随访。一个概念出现了，即远离肿瘤的全身免疫事件反映了局部对免疫治疗的反应或耐药性。这种癌症“宏观环境”的重要性已经在一些前沿的临床前报告中得到了证明，并且在接受 ICI 治疗的患者中出现的有趣数据也得到了证实。在这篇综述中，我们将提供基于血液免疫细胞标志物在指导免疫治疗合格的 NSCLC 患者治疗决策方面的潜在生物学依据。最后，我们将描述新的技术，这些技术将有助于发现更多具有成为预测性生物标志物潜力的免疫细胞亚群，并思考在不久的将来将这种分析方法引入常规临床护理的方法和剩余挑战。
