Exploiting Tertiary Lymphoid Structures to Stimulate Antitumor Immunity and Improve Immunotherapy Efficacy

Abstract

Tumor-associated tertiary lymphoid structures (TLS) have been associated with favorable clinical outcomes and response to immune checkpoint inhibitors in many cancer types, including non-small cell lung cancer. Although the detailed cellular and molecular mechanisms underlying these clinical associations have not been fully elucidated, growing preclinical and clinical studies are helping to elucidate the mechanisms at the basis of TLS formation, composition, and regulation of immune responses. However, a major challenge remains how to exploit TLS to enhance naïve and treatment-mediated antitumor immune responses. Here, we discuss the current understanding of tumor-associated TLS, preclinical models that can be used to study them, and potential therapeutic interventions to boost TLS formation, with a particular focus on lung cancer research.

Lymphocyte homing and recirculation with tumor tertiary lymphoid structure formation: predictions for successful cancer immunotherapy

“…TLSs are ectopically formations that mimic the secondary lymphoid organs (SLOs), consisting of lymphocytes and antigen-presenting cells (APCs) assembled structurally. Cancer patients with TLSs tend to have more favorable outcomes and enhanced responses to immunotherapies in several studies ( 7 , 8 ). As lymphoid structures formed in chronic inflammatory tumor sites, TLSs share some structural and functional features with TdLNs and are remarkable for supporting tumor immune response.…”