CD103+ cDC1 vaccine efficacy in murine breast cancer is inhibited by STAT3

• DOI: 10.4049/jimmunol.204.supp.169.16
• Publication Date: 2023-01-01T11:29:28Z
• Authors: Taylor T Chrisikos; Yifan Zhou; Haiyan S Li; Rachel Lauren Bab...; Xianxiu Wan; Bhakti Patel; Kathryn Newton; James Mancuso; Stephanie S Watowich
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract Conventional dendritic cells (cDCs) are a crucial immune population, which includes multiple subtypes that coordinate adaptive immunity and tolerance. Migratory type 1 cDC1s (CD103+ in mice) required to induce CD8+ T cell-mediated anti-tumor immunity, yet whether how tumors regulate CD103+ cDC1 function is largely unknown. Many tumor-associated immunosuppressive cytokines, such as interleukin (IL)-10, require Signal Transducer Activator of Transcription 3 (STAT3) for intracellular signaling; therefore, we sought determine STAT3 inhibits cDC1-mediated immunity. Indeed, found vitro-derived STAT3-deficient (Stat3Δ/Δ) cDC1sare resistant IL-10 – mediated inhibition Toll-like receptor (TLR3)-agonist induced maturation. When used an vaccine, Stat3Δ/Δ inhibited breast tumor growth increased mouse survival greater degree than STAT3-sufficient cDC1s. Vaccination with antigen-specific IFN-g+ CD4+ tumor-draining lymph nodes compared controls. Moreover, receptor-deficient restrained effectively Taken together, our results demonstrate suppresses maturation vaccine efficacy cancer. The data also suggest important factor the murine mammary environment mediating signaling Thus, may provide effective strategy improving cDC1-based vaccines.