Tertiary lymphoid structures for anti-tumor immunotherapy

Tertiary lymphoid structures (TLSs) are transient ectopic lymphoid-like structures potentiating the adaptive anti-tumor immunotherapy efficiency. They have been observed across diverse malignancies since they were initially found to correlate with favorable prognosis in non-small cell lung cancer. Importantly, TLSs could systematically enhance immune responses efficiency by optimizing the immune ecology of the tumor microenvironmen (TME). They have attracted considerable interest as predictive biomarkers for anti-tumor treatment responses, including immune checkpoint blockade (ICB) and potential chemotherapy. However, TLSs formation within tumor is poorly controllable, and lacks effective strategies for precisely modulating their formation and function. In this comprehensive review, we first summarize the composition and formation mechanism of TLSs. Second, we address the role of TLSs in enhancing anti-tumor immunotherapy efficiency. Third, we explore the advanced methods to modulate TLSs formation. Finally, we summarize novel multifunctional materials in facilitating TLSs formation to enhance anti-tumor immunotherapy both in basic and clinical. Deep understanding of the formation mechanism and role of TLSs could provide insights into modulation of TLSs for improving anti-tumor immunotherapy efficiency.