Tertiary lymphoid structure can be a potential therapeutic target for head and neck squamous cell carcinoma (Review).

Tertiary lymphoid structure (TLS) is a kind of ectopic lymphoid tissues that form in chronic inflammation or tumor microenvironment (TME) and is structurally similar to secondary lymphoid organs such as lymph nodes, containing B cell follicles, T cell regions, and mature dendritic cells. It was reported that TLS is associated with improved prognosis and higher response rates to immunotherapy in a variety of tumors. However, the mechanism of TLS and its clinical significance in head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, the latest advances of biological characteristics, research progress of TLS and its role in the TME were summarized. The relationship between the prognosis and response to immunotherapy of distinct cancers and the location, density and maturity of TLS were addressed. Predictive, therapeutic and prognostic values of TLS in HNSCC were also reviewed. In addition, the therapeutic value of TLS and the potential strategies for patients with HNSCC by regulating TLS were also discussed. Collectively, TLS can be regarded as an independent predictive biomarker for immunotherapy in HNSCC and appears to have a close correlation with the prognosis of HNSCC. Despite little acknowledge of mechanisms and few preclinical/clinical trials on TLS-targeted therapy, TLS-based therapy can provide a new potential therapeutic strategy.