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Tertiary Lymphoid Structures: Allies of Cancer Immunotherapy
Xinze Li1,2, Xinnan Zhang1,2, Zhiyong Cao1,2
1School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
Immunology
|July 24, 2025
Summary
Tertiary lymphoid structures (TLSs) are crucial for enhancing cancer immunotherapy responses. This review synthesizes data on TLS composition and function, highlighting their potential to improve patient outcomes.
Area of Science:
- Immunology
- Oncology
- Translational Research
Background:
- Immunotherapy shows promise in cancer treatment but benefits only a subset of patients.
- Tertiary lymphoid structures (TLSs), immune aggregates in non-lymphoid tissues, are increasingly recognized for their role in anti-cancer immunity.
- A comprehensive synthesis of clinical and preclinical data on TLSs in cancer immunotherapy is lacking.
Purpose of the Study:
- To systematically review the composition and heterogeneity of TLSs.
- To elucidate the mechanisms by which TLSs influence cancer immunotherapy outcomes.
- To explore strategies for targeting TLSs to enhance therapeutic responses.
Main Methods:
- Systematic review of existing clinical and preclinical literature.
- Analysis of TLS composition, including T follicular helper cells and germinal center B cells.
- Evaluation of the impact of various agents (pharmacological, viral, biomaterials) on TLS formation and function.
Main Results:
- TLS composition and heterogeneity significantly impact cancer immunotherapy efficacy.
- T follicular helper cells drive the selection of high-affinity B cells, crucial for antibody production within TLSs.
- Pharmacological agents, oncolytic viruses, AAVs, and biomaterials can modulate TLSs to enhance responses to immune checkpoint inhibitors.
Conclusions:
- TLSs are critical determinants of response to cancer immunotherapy.
- Targeting TLSs represents a promising strategy to improve durable clinical responses in cancer patients.
- Further research into TLS modulation holds significant translational potential for oncology.
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