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Review
. 2024 Apr 16:15:1369626.
doi: 10.3389/fimmu.2024.1369626. eCollection 2024.

Tertiary lymphoid structures in cancer: maturation and induction

Yulu Chen  1   2   3 , Yuhao Wu  1   2   3 , Guorong Yan  1   2   3 , Guolong Zhang  1   2   3
Affiliations
Review

Tertiary lymphoid structures in cancer: maturation and induction

Yulu Chen et al. Front Immunol. .

Abstract

Tertiary lymphoid structure (TLS) is an ectopic lymphocyte aggregate formed in peripheral non-lymphoid tissues, including inflamed or cancerous tissue. Tumor-associated TLS serves as a prominent center of antigen presentation and adaptive immune activation within the periphery, which has exhibited positive prognostic value in various cancers. In recent years, the concept of maturity regarding TLS has been proposed and mature TLS, characterized by well-developed germinal centers, exhibits a more potent tumor-suppressive capacity with stronger significance. Meanwhile, more and more evidence showed that TLS can be induced by therapeutic interventions during cancer treatments. Thus, the evaluation of TLS maturity and the therapeutic interventions that induce its formation are critical issues in current TLS research. In this review, we aim to provide a comprehensive summary of the existing classifications for TLS maturity and therapeutic strategies capable of inducing its formation in tumors.

Keywords: cancer treatment; immunotherapy; maturity; tertiary lymphoid structure; tumor microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Formation of tertiary lymphoid structure. The formation of tertiary lymphoid structure (TLS) is a response to inflammatory stimulation mediated by different cytokines, and it can be divided into three steps: (i) interaction of lymphoid tissue inducer cells (LTi) and lymphoid tissue organizers (LTo); (ii) high endothelial venules (HEV) formation and immune cells recruitment; (iii) T/B compartmentalization and germinal centers (GC) formation. Created with BioRender.com.
Figure 2
Figure 2
Maturity classification of tertiary lymphoid structure. The defining criterion for mature tertiary lymphoid structure (TLS) is germinal centers (GC) formation. It can be further classified according to morphology or follicular dendritic cells (FDC)/GC-B cell markers. Created with BioRender.com.
Figure 3
Figure 3
The induction of tertiary lymphoid structures. Cancer treatments promote the formation of tertiary lymphoid structures (TLS) mainly including immunotherapy, chemoradiotherapy, injection of TLS-associated cytokines and chemokines, activation of TLS-associated proteins and signaling pathways and some potential therapeutic approaches such as microbial transplantation and exogenous vesicle injection. Created with BioRender.com.
See this image and copyright information in PMC

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