184P Alterations in tumorigenicity and immunogenicity of bladder cancer cells after somatic cell reprogramming

vivo antitumor immune effects and microbiota diversity induced by BP conjugated with PDAC-associated peptide antigens MHCI/II ([BP-MHCI/II]) in combination with an ICI and a FAK inhibitor (FAKi).Methods: BP were conjugated with MHCI and MHCII-PDAC peptides.To assess the impact of the nanoconjugate on orthotopic PDAC tumor growth, KPC cells were implanted in the pancreas of mice.On day 7, mice were immunized with two doses of either PBS, free antigens/adjuvants (MHCI/MHCII antigens + Toll-like receptor ligands), or [BP-MHCI/II] mixed with adjuvants and combined with ICI and FAKi.Mice weight was monitored regularly.On day 20, PDAC tumors were collected.Functional markers of tumor-infiltrating immune cells were quantified by FACS, and gut and tumor-associated microbiota diversity was analyzed through 16S metagenomic sequencing, followed by QIIME2.11bioinformatic tools.Results: [BP-MHCI/II] exhibited a mean diameter of 40 nm and a zeta potential (ZP) of -25 mV, with MHCI and MHCII peptide loading efficiencies of 20% and 13%, respectively.Tumor reduction was more pronounced in mice treated with [BP-MHCI/ II] in combination with ICI and FAKi, compared to PBS.The combination treatment modulated tumor-infiltrating immune cells promoting antitumor immunity.Also, gut and tumor microbiota composition and diversity varied among treatments. Conclusions:The combination of [BP-MHCI/II] with ICI and FAKi represents a promising strategy to overcome tumor growth, to modulate immune cells in tumor microenvironment and microbiota composition in PDAC.