Tertiary lymphoid structures (TLSs) form under chronic inflammation in some tumors and have been associated with favorable prognosis and clinical benefit in response to therapy. In this review, Sautes-Fridman et al. describe the formation, composition, structure, and function of TLSs in primary and metastatic tumors. Current research is aimed at understanding how TLSs promote tumor antigen presentation, T and B cell maturation and infiltration into tumors, and antibody production. Efforts to induce TLSs include the use of chemokines, cytokines, antibodies, antigen-presenting cells, and synthetic scaffolds.
Tertiary lymphoid structures (TLSs) are ectopic lymphoid organs that develop in non-lymphoid tissues at sites of chronic inflammation including tumours. Key common characteristics between secondary lymphoid organogenesis and TLS neogenesis have been identified. TLSs exist under different maturation states in tumours, culminating in germinal centre formation. The mechanisms that underlie the role of TLSs in the adaptive antitumour immune response are being deciphered. The description of the correlation between TLS presence and clinical benefit in patients with cancer, suggesting that TLSs could be a prognostic and predictive factor, has drawn strong interest into investigating the role of TLSs in tumours. A current major challenge is to exploit TLSs to promote lymphocyte infiltration, activation by tumour antigens and differentiation to increase the antitumour immune response. Several approaches are being developed using chemokines, cytokines, antibodies, antigen-presenting cells or synthetic scaffolds to induce TLS formation. Strategies aiming to induce TLS neogenesis in immune-low tumours and in immune-high tumours, in this case, in combination with therapeutic agents dampening the inflammatory environment and/or with immune checkpoint inhibitors, represent promising avenues for cancer treatment.