Yang Man, Che Yurou, Li Kezhen, Fang Zengyi, Li Simin, Wang Mei, Zhang Yiyao, Xu Zhu, Luo Liping, Wu Chuan, Lai Xin, Wang Weidong
Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610000, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu 610000, China.
J Zhejiang Univ Sci B. 2023;24(9):779-795. doi: 10.1631/jzus.B2200605.
Tumor-associated tertiary lymphoid structures (TLSs) are ectopic lymphoid formations within tumor tissue, with mainly B and T cell populations forming the organic aggregates. The presence of TLSs in tumors has been strongly associated with patient responsiveness to immunotherapy regimens and improving tumor prognosis. Researchers have been motivated to actively explore TLSs due to their bright clinical application prospects. Various studies have attempted to decipher TLSs regarding their formation mechanism, structural composition, induction generation, predictive markers, and clinical utilization. Meanwhile, the scientific approaches to qualitative and quantitative descriptions are crucial for TLS studies. In terms of detection, hematoxylin and eosin (H&E), multiplex immunohistochemistry (mIHC), multiplex immunofluorescence (mIF), and 12-chemokine gene signature have been the top approved methods. However, no standard methods exist for the quantitative analysis of TLSs, such as absolute TLS count, analysis of TLS constituent cells, structural features, TLS spatial location, density, and maturity. This study reviews the latest research progress on TLS detection and quantification, proposes new directions for TLS assessment, and addresses issues for the quantitative application of TLSs in the clinic.
肿瘤相关三级淋巴结构（TLSs）是肿瘤组织内的异位淋巴组织，主要由B细胞和T细胞群体形成有机聚集体。肿瘤中TLSs的存在与患者对免疫治疗方案的反应以及改善肿瘤预后密切相关。由于其广阔的临床应用前景，研究人员一直积极探索TLSs。各种研究试图从其形成机制、结构组成、诱导产生、预测标志物和临床应用等方面解读TLSs。同时，定性和定量描述的科学方法对于TLS研究至关重要。在检测方面，苏木精和伊红（H&E）染色、多重免疫组织化学（mIHC）、多重免疫荧光（mIF）和12种趋化因子基因特征是最常用的方法。然而，对于TLSs的定量分析尚无标准方法，如绝对TLS计数、TLS组成细胞分析、结构特征、TLS空间位置、密度和成熟度等。本研究综述了TLS检测和定量的最新研究进展，提出了TLS评估的新方向，并探讨了TLS在临床定量应用中的问题。
