Multiple mechanisms and applications of tertiary lymphoid structures and immune checkpoint blockade

BACKGROUND: Immune checkpoint blockade (ICB) inhibits tumor immune escape and has significantly advanced tumor therapy. However, ICB benefits only a minority of patients treated and may lead to many immune-related adverse events. Therefore, identifying factors that can predict treatment outcomes, enhance synergy with ICB, and mitigate immune-related adverse events is urgently needed. MAIN TEXT: Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues that arise from the tumor periphery. They have been found to be associated with better prognosis and improved clinical outcomes after ICB therapy. TLS may help address the problems associated with ICB. The multiple mechanisms of action between TLS and ICB remain unknown. This paper described potential mechanisms of interaction between the two and explored their potential applications.