Abstract IA06: Isotype-Switched Antibodies Produced in Tertiary Lymphoid Structures Antagonize Human Cancer Progression

Abstract Many epithelial cancers orchestrate prognostically significant intra-tumoral tertiary lymphoid structures (TLS), yet the mechanisms behind their antitumor activity remain unclear. Here we show that intra-tumoral TLS in human cancers contain highly oligoclonal B cells and plasma cells expressing IgA or IgG, which are not found outside the TLS. We demonstrate that these antibodies antagonize the progression of the autologous tumor. Accordingly, TLS enlargement and de novo formation in response to the injection of an oncolytic virus in muscle-invasive, cisplatin-ineligible bladder cancers is associated with complete clincial responses and the production of IgA and IgG antibodies at tumor beds. Our data show that TLS inhibit malignant progression through in situ production of isotype-switched anti-tumor antibodies , underscoring the importance of coordinated cellular and humoral responses in human cancer. Citation Format: Jose R Conejo-Garcia. Isotype-Switched Antibodies Produced in Tertiary Lymphoid Structures Antagonize Human Cancer Progression [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr IA06.