白细胞介素 6 驱动针对胰腺癌的持久 T 细胞介导免疫

We overexpressed IL-6 in multiple Kras G12D/+ , Tp53 R172H/+, Pdx1-Cre (KPC) cell lines, which were orthotopically implanted in mice (OT-PDAC IL6 ). We followed mouse survival and measured tumor growth, tumor histology, and plasma IL-6 at 5 and 10 days after tumor implantation. We measured tumor immune cell infiltration via flow cytometry and histology. We used antibody-based T cell depletion and secondary tumor implantation rechallenge to test the dependency of the durable immune reaction on T cells.

Improved survival occurred in all instances of OT-PDAC IL6 , with one cell line (KxPxCx) reproducibly resulting in long-term recurrence-free survival. With KxPxCx cells, circulating IL-6 was 100-fold higher in OT-PDAC IL6 than in OT-PDAC parental mice. Flow cytometry revealed increased T cells and NK cells, and decreased T regulatory cells, and we observed significantly increased lymphoid aggregates in OT-PDAC IL6 as compared to OT-PDAC parental tumors. Antibody-based CD4 + and CD8 + T cell depletion prevented tumor clearance and completely abolished the survival advantage in OT-PDAC IL6 mice. The anti-tumor immune response to OT-PDAC IL6 rendered mice immune to re-challenge with OT-PDAC parental tumors.

Locally high IL-6 concentrations potently enhance the T cell-mediated anti-tumor response to PDAC.