Mature tertiary lymphoid structures: important contributors to anti-tumor immune efficacy

Xinyu Bao; Xuwen Lin; Mei Xie; Jie Yao; Jialin Song; Xidong Ma; Xin Zhang; Yinguang Zhang; Yiming Liu; Wenya Han; Yiran Liang; Hongling Hu; Li Xu; Xinying Xue

doi:10.3389/fimmu.2024.1413067

Mature tertiary lymphoid structures: important contributors to anti-tumor immune efficacy

Front Immunol. 2024 Jul 4:15:1413067. doi: 10.3389/fimmu.2024.1413067. eCollection 2024.

Authors

Xinyu Bao^#¹, Xuwen Lin^#², Mei Xie³, Jie Yao², Jialin Song¹, Xidong Ma², Xin Zhang¹, Yinguang Zhang⁴, Yiming Liu⁵, Wenya Han⁶, Yiran Liang², Hongling Hu⁷, Li Xu⁸, Xinying Xue^{1

2}

Affiliations

¹ Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, Weifang, China.
² Department of Respiratory and Critical Care, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
³ Department of Respiratory and Critical Care, Chinese PLA General Hospital, Beijing, China.
⁴ Department of Thoracic Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁵ Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
⁶ Department of Respiratory and Critical Care, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
⁷ Department of Respiratory Medicine, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁸ Department of Respiratory Endoscopy, The Public Health Clinical Center Affiliated of Shandong University, Jinan, China.

^# Contributed equally.

Abstract

Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.

Keywords: B cell; germinal center; mature tertiary lymphoid structure; prognosis; tumor immunotherapy.

Publication types

Review

MeSH terms

Animals
B-Lymphocytes / immunology
Humans
Immunotherapy / methods
Neoplasms* / immunology
Neoplasms* / pathology
Neoplasms* / therapy
T-Lymphocytes / immunology
Tertiary Lymphoid Structures* / immunology
Tertiary Lymphoid Structures* / pathology
Tumor Microenvironment* / immunology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (62176166, 62076254), Capital Medical University Affiliated Beijing Shijitan Hospital Talent Training Program during the "14th Five-Year” Plan period" (2023DTRXXY), and Capital Medical University Outstanding Young Talent Program (A2310).