Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates formed in non-lymphoid tissues, including inflamed or cancerous tissue. TLS serve as key sites for antigen presentation and adaptive immune activation in the tumor microenvironment (TME), with positive prognostic implications in various cancers. Recent research has highlighted the importance of TLS maturity, characterized by well-developed germinal centers, which exhibit stronger tumor-suppressive capacity. TLS can be induced by various cancer treatments, including immunotherapy, chemoradiotherapy, cytokines, agonists, inhibitors, and other potential therapies. TLS maturity is crucial for evaluating treatment efficacy and is associated with improved prognosis in cancer patients. TLS formation involves three steps: interaction of lymphoid tissue inducer cells (LTi) and lymphoid tissue organizers (LTo), HEV formation and immune cell recruitment, and T/B compartmentalization and GC formation. TLS detection relies on pathological methods such as HE staining, IHC, and IF, as well as gene signatures like the 12-chemokines signature. TLS maturity is assessed by the presence of GC, with mature TLS showing enhanced immune function. TLS can be induced by various treatments, including immunotherapy, cytokines, and combination therapies. TLS formation is associated with improved treatment outcomes, and its maturity is a critical factor in cancer immunotherapy. Future research should focus on understanding TLS mechanisms, improving TLS maturity, and developing targeted therapies for cancer.Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates formed in non-lymphoid tissues, including inflamed or cancerous tissue. TLS serve as key sites for antigen presentation and adaptive immune activation in the tumor microenvironment (TME), with positive prognostic implications in various cancers. Recent research has highlighted the importance of TLS maturity, characterized by well-developed germinal centers, which exhibit stronger tumor-suppressive capacity. TLS can be induced by various cancer treatments, including immunotherapy, chemoradiotherapy, cytokines, agonists, inhibitors, and other potential therapies. TLS maturity is crucial for evaluating treatment efficacy and is associated with improved prognosis in cancer patients. TLS formation involves three steps: interaction of lymphoid tissue inducer cells (LTi) and lymphoid tissue organizers (LTo), HEV formation and immune cell recruitment, and T/B compartmentalization and GC formation. TLS detection relies on pathological methods such as HE staining, IHC, and IF, as well as gene signatures like the 12-chemokines signature. TLS maturity is assessed by the presence of GC, with mature TLS showing enhanced immune function. TLS can be induced by various treatments, including immunotherapy, cytokines, and combination therapies. TLS formation is associated with improved treatment outcomes, and its maturity is a critical factor in cancer immunotherapy. Future research should focus on understanding TLS mechanisms, improving TLS maturity, and developing targeted therapies for cancer.