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The combination of a stimulator of interferon genes (STING) agonist and a lymphotoxin beta receptor (LTβR) agonist is an experimental immunotherapy regimen designed to promote the formation of tertiary lymphoid structures (TLS) within the tumor microenvironment. STING is an intracellular sensor that triggers type I interferon production, while LTβR is a member of the tumor necrosis factor receptor superfamily involved in lymphoid organogenesis. By simultaneously activating these pathways, the therapy induces mature, germinal center-rich TLS that facilitate B cell maturation, antibody-dependent cellular cytotoxicity (ADCC), and robust CD8+ T cell responses. This approach has demonstrated the ability to convert immune-cold tumors, such as pancreatic ductal adenocarcinoma and rhabdomyosarcoma, into immune-hot environments, enhancing the efficacy of PD-1/PD-L1 checkpoint inhibitors and providing long-term protection against tumor recurrence in preclinical models.
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