From heterogeneity to prognosis: understanding the complexity of tertiary lymphoid structures in tumors

Abstract

Tertiary lymphoid structures (TLSs) are aberrant lymphoid tissues found in persistent inflammatory settings, including malignancies, autoimmune disorders, and transplanted organs. The organization and architecture of TLS closely resemble that of secondary lymphoid organs (SLOs). The formation of TLS is an ongoing process, with varying structural features observed at different stages of maturation. The tumor microenvironment (TME) is a multifaceted milieu comprising cells, molecules, and extracellular matrix components in close proximity to the neoplasm. TLS within the TME have the capacity to actively elicit anti-tumor immune responses. TLSs exhibit tumor-specific and individual-specific characteristics, leading to varying immune responses towards tumor immunity based on their distinct cellular components, maturity levels, and spatial distribution. Cell interaction is the foundational elements of tumor immunity. Despite differences in the cellular composition of TLS, B cells and T cells are the main components of tumor-associated TLS。Recent research has highlighted the significance of diverse subtypes of B cells and T cells within TLSs in influencing the therapeutic outcomes and prognostic indicators of individual tumors. This review elucidates the diversity of TLS in terms of cellular composition, developmental stage, anatomical location, and the influence of cytokines on their initiation and progression. Furthermore, the article examines the involvement of B and T cells within TLS and the significance of TLS in relation to tumor prognosis.

Keywords: Cytokines; Heterogeneity; Prognosis; Tertiary lymphoid structure; Tumor.