Pancreatic cancer cells overexpressing interleukin 6 induce T-cell-mediated tumor clearance and durable anti-tumor immune response.

Tumor immune resistance is recognized as a contributor to low survivorship in pancreatic ductal adenocarcinoma (PDAC). We developed a novel murine model of spontaneous PDAC clearance, generated by overexpressing interleukin-6 (IL-6) in orthotopically implanted PDAC cancer cells (OT-PDAC). Circulating IL-6 was 100-fold higher in OT-PDAC than in OT-PDAC mice. OT-PDAC tumors were present at 5 days post-implantation, and undetectable by 10 days post implantation. Flow cytometry revealed increased T cells and NK cells, and decreased T regulatory cells in OT-PDAC as compared to OT-PDAC tumors. Increased lymphoid aggregates were apparent by histological assessment and may account for elevated T cell content. Antibody-based depletion of CD4 and CD8 T cells prevented tumor clearance and significantly reduced survival of OT-PDAC mice. The anti-tumor immune response to OT-PDAC rendered mice immune to re-challenge with OT-PDAC tumors. In high concentrations, IL-6 acts in opposition to previously described pro-tumorigenic effects by enhancing the T cell-mediated anti-tumor response to PDAC.