# Initiation of Tertiary Lymphoid Structures for Cancer Immunotherapy

## TL;DR

This paper reviews how tertiary lymphoid structures form in tumors and how they can be used to improve cancer immunotherapy.

## Contribution

The paper systematically summarizes the triggers and signaling networks involved in TLS initiation and their role in cancer immunotherapy.

## Key findings

- TLS initiation is regulated by lymphoid tissue inducer and organizer cells through cytokines and chemokines.
- TLSs enhance antitumor immune responses by reshaping the tumor microenvironment and recruiting immune cells.
- Modulating TLS initiation presents new strategies for cancer immunotherapy.

## Abstract

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates formed by lymphocytes and antigen-presenting cells within chronic inflammatory microenvironments or tumor microenvironments (TMEs), and their initiation phase is a critical step for mounting an effective antitumor immune response. TLS initiation depends on the interplay between lymphoid tissue inducer cells and lymphoid tissue organizer cells and is finely regulated by multiple cytokines and chemokines. This review systematically summarizes the key triggers and signaling networks driving TLS initiation, elucidating how TLSs reshape the TMEs, facilitate antigen presentation, and recruit immune cells to enhance antitumor immune responses. Furthermore, potential strategies to modulate TLS initiation are discussed, along with the emerging role of TLSs as promising targets in cancer immunotherapy.