Detection and quantitative analysis of tumor-associated tertiary lymphoid structures

Man YANG; Yurou CHE; Kezhen LI; Zengyi FANG; Simin LI; Mei WANG; Yiyao ZHANG; Zhu XU; Liping LUO; Chuan WU; Xin LAI; Weidong WANG

doi:10.1631/jzus.B2200605

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Review | Updated：2023-09-13

Detection and quantitative analysis of tumor-associated tertiary lymphoid structures
Detection and quantitative analysis of tumor-associated tertiary lymphoid structures
肿瘤相关的三级淋巴结构的检测和量化分析
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 24, Issue 9, Pages: 779-795(2023)
Affiliations：

1.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
2.School of Medicine, University of Electronic Science and Technology of China, Chengdu 610000, China
3.Department of Oncology, School of Clinical Medicine, Southwest Medical University, Luzhou 646000, China
Funds：
DOI：10.1631/jzus.B2200605
CLC：
CSTR：

Man YANG, Yurou CHE, Kezhen LI, et al. Detection and quantitative analysis of tumor-associated tertiary lymphoid structures. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 24(9):779-795(2023)
DOI：

Man YANG, Yurou CHE, Kezhen LI, et al. Detection and quantitative analysis of tumor-associated tertiary lymphoid structures. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 24(9):779-795(2023) DOI： 10.1631/jzus.B2200605.

摘要

肿瘤相关的三级淋巴结构（TLS），主要由B细胞和T细胞群体有机聚集形成于肿瘤组织范围内的异位淋巴组织。在肿瘤中，TLS的存在与免疫治疗的反应性和肿瘤预后密切相关。因其具有广阔的临床应用前景，研究者一直在积极探索。许多研究都试图破译TLS的形成机制、结构组成、诱导生成、预测标记物和临床利用。与此同时，用科学的方法定性和定量描述TLS，对其研究至关重要。在检测方面，苏木精-伊红染色法（H&E）染色、多重免疫组化、多重免疫荧光和12趋化因子基因特征是被认可的方法。然而在TLS的定量分析方面，例如TLS的绝对计数、组成TLS的细胞分析、TLS的结构特征、空间位置、密度、成熟度等，目前尚无标准方法。本研究回顾了TLS检测和定量分析的最新研究进展，提出了TLS评估的新方向，并解决了TLS在临床上的定量应用问题。

Abstract

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.

关键词

三级淋巴结构（TLS）肿瘤微环境趋化因子特征空间转录组学人工智能影像组学

Keywords

Tertiary lymphoid structureTumor microenvironmentChemokine signatureSpatial omicsArtificial intelligenceRadiomics

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