Tertiary lymphoid structures as biomarkers and therapeutic targets in neoadjuvant cancer immunotherapy.

Neoadjuvant immunotherapy is reshaping the treatment of resectable solid tumors, but biomarkers that reflect spatially organized antitumor immunity remain limited. Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that support local antigen presentation, lymphocyte recruitment, T-B cell interaction, germinal center reactions and humoral immunity. Increasing evidence suggests that TLS density, maturation, localization and cellular composition are associated with immune checkpoint blockade response, pathological regression and prognosis. Beyond their biomarker value, TLS may represent modifiable immune niches that can be induced or remodeled by checkpoint blockade, chemotherapy, radiotherapy, vaccines and stromal-vascular strategies. This mini-review discusses the biological basis, biomarker potential, therapeutic targeting and clinical translation of TLS in neoadjuvant cancer immunotherapy, highlighting key challenges and future TLS-guided trial designs.