三级淋巴结构作为NSCLC新辅助化学免疫治疗的预测因子和靶点
TLS as Predictors and Targets in Neoadjuvant Chemoimmunotherapy for NSCLC.
作者
作者单位
- Cancer Research Center, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
- Department of Pathology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
摘要
中文
三级淋巴结构（TLS）已成为非小细胞肺癌（NSCLC）抗肿瘤免疫的关键调节因子，越来越多的证据支持其作为新辅助化学免疫治疗中预后生物标志物和功能靶点的作用。TLS是有组织的异位淋巴聚集体，促进肿瘤微环境内的局部抗原呈递、T和B细胞活化以及记忆免疫应答。它们的存在和成熟状态与良好的临床结局和对免疫检查点抑制剂增强的反应性相关。尽管有这些见解，仍有几个障碍阻碍临床转化。目前的方法在动态监测治疗期间TLS演变方面仍然有限，潜在的免疫调节机制——特别是免疫亚群、基质成分和肿瘤细胞之间的相互作用——尚未完全阐明。此外，转化面临挑战，包括机构间变异性、缺乏标准化评估标准以及需要多中心前瞻性验证。整合多模态技术——高复合成像、空间转录组学和数字病理学——与基于AI的平台，有望实现精细的TLS表征和实时监测。近期优先事项包括优化动态监测技术和建立标准化评分系统。中长期优先事项包括多中心试验以验证TLS在不同人群中的效用，识别TLS形成的新驱动因素，以及开发利用TLS作为预测性生物标志物和治疗靶点的优化联合免疫治疗方案。通过桥接基础免疫学和临床肿瘤学，TLS有望成为精准癌症免疫治疗中的关键调节节点，这可能促进NSCLC新辅助治疗格局的范式转变，实现涵盖预测、干预和动态疗效优化的全周期闭环管理框架。
English
Tertiary lymphoid structures (TLS) have emerged as critical modulators of antitumor immunity in non-small cell lung cancer (NSCLC), with growing evidence supporting their role as both prognostic biomarkers and functional targets in neoadjuvant chemoimmunotherapy. TLS are organized ectopic lymphoid aggregates that facilitate local antigen presentation, T and B cell activation, and memory immune responses within the tumor microenvironment. Their presence and maturation status correlate with favorable clinical outcomes and enhanced responsiveness to immune checkpoint inhibitors. Despite these insights, several obstacles hinder clinical translation. Current approaches remain limited in dynamically monitoring TLS evolution during treatment, and the underlying immunoregulatory mechanisms-particularly interactions among immune subsets, stromal components, and tumor cells-are not fully elucidated. Additionally, translation faces challenges including inter-institutional variability, lack of standardized assessment criteria, and the need for multi-center prospective validation. Integrating multimodal technologies-high-plex imaging, spatial transcriptomics, and digital pathology-with AI-based platforms holds promise for refined TLS characterization and real-time monitoring. Near-term priorities include optimizing dynamic monitoring techniques and establishing standardized scoring systems. Medium-to-long-term priorities encompass multi-center trials to validate TLS utility across diverse populations, identify novel drivers of TLS formation, and develop optimized combinatorial immunotherapy regimens that leverage TLS as both predictive biomarkers and therapeutic targets. By bridging basic immunology and clinical oncology, TLS are poised to emerge as key regulatory nodes in precision cancer immunotherapy, which may catalyze a paradigm shift in the neoadjuvant NSCLC landscape, enabling a closed-loop management framework encompassing prediction, intervention, and dynamic efficacy optimization across the entire continuum of patient care.
分类与指标
- 研究类型
- 综述Meta
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 2.6
- 新锐分区
- 4区