Mature tertiary lymphoid structure (Mature TLS)

Mature tertiary lymphoid structures (TLS) are organized, ectopic lymphoid aggregates that form in non-lymphoid tissues during chronic inflammation, most notably within the tumor microenvironment (Sautès-Fridman et al., Nature Reviews Cancer, 2019). Unlike immature TLS, mature TLS are characterized by the presence of active germinal centers containing follicular dendritic cells and proliferating B cells, which facilitate local affinity maturation and class-switch recombination (Dieu-Nosjean et al., Trends in Immunology, 2016). In oncology, the presence of mature TLS is a robust positive prognostic indicator and is strongly associated with improved clinical responses to immune checkpoint inhibitors, such as PD-1 and CTLA-4 blockers (Helmink et al., Nature, 2020; Cabrita et al., Nature, 2020). These structures serve as local 'hubs' for the generation of tumor-specific T and B cell responses, bypassing the need for systemic recruitment from secondary lymphoid organs. Conversely, in autoimmune diseases like rheumatoid arthritis or Sjögren's syndrome, mature TLS can exacerbate pathology by promoting the production of autoantibodies (Pitzalis et al., Nature Reviews Rheumatology, 2014). Current therapeutic strategies aim to induce or stabilize mature TLS using chemokines like CXCL13 or STING agonists to convert 'cold' tumors into 'hot' tumors, thereby enhancing the efficacy of immunotherapy.

Other names

Tertiary lymphoid organTLOEctopic lymphoid structureELSGerminal center-positive tertiary lymphoid structureMature ectopic lymphoid structure

Induction and stabilization of organized ectopic lymphoid aggregates to facilitate local adaptive immune responses and enhance intratumoral lymphocyte infiltration.