Role of tertiary lymphoid structures in the tumour microenvironment and immunotherapy response of renal cell carcinoma

Abstract

In the tumour microenvironment (TME) of renal cell carcinoma (RCC), tertiary lymphoid structures (TLS) play a crucial role in anti-tumour immune responses. Resembling secondary lymphoid organs, TLS comprises B cells, T cell zones, high endothelial venules, and antigen-presenting cells, facilitating local immune activation. While TLS has shown correlations with improved immune checkpoint inhibitors (ICIs) outcomes in other cancers, its role in RCC is still under investigation. Emerging evidence indicates that mature TLS enhances anti-tumour activity by activating T and B cells, whereas immature TLS may contribute to immune suppression. The RCC TME is highly immunosuppressive, marked by regulatory T cells, myeloid-derived suppressor cells, and elevated pro-angiogenic and immunosuppressive cytokines. In this context, TLS, particularly mature TLS, can counteract immunosuppression, boost local immune responses, and improve ICIs efficacy. However, TLS in RCC is heterogeneous, with their formation and function affected by factors like CXCL13 expression. The presence, maturity, and functionality of TLS may serve as valuable predictors of ICIs response and patient prognosis. Further research is required to understand TLS regulation and leverage their potential to enhance personalised immunotherapy for RCC.