Abstract 6679: MicroRNA cargo of extracellular vesicles of pancreatic cancer patients have immunoregulatory potential

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dismal five-year survival rate of 5-8%. Extracellular vesicles (EVs), nano-sized membrane-bound particles (30-150 nm) present in the circulatory system, play a crucial role in mediating intercellular communication, regulating immune responses, and driving tumor progression. MicroRNAs (miRNAs), integral components of EVs, function as key mediators in cellular signaling pathways. Although the role of exosomal miRNAs (exo-miRNAs) in cancer pathogenesis is well established, their comprehensive therapeutic, diagnostic, and immunomodulatory potential remains largely unexplored. This study established the differential exoMIR profile of PDAC patients using small RNA sequencing on the Illumina platform, compared with healthy controls, post-surgery and follow-up. Statistical analysis revealed hsa-miR-375-3p, hsa-miR-134-5p and hsa-miR-197-3p miRNAs were downregulated in PDAC patients than controls whereas hsa-miR-126-5p, hsa-miR-7847-3p, hsa-miR-197-3p were upregulated post-surgery. Six-month follow-up sample after surgery had hsa-miR-144-3p, hsa-miR-194-5p, hsa-miR-16-5p, hsa-miR-197-5p upregulated and hsa-miR-125b-3p was downregulated as compared to post-surgery sample. These distinct exoMIRs were identified as key regulators of cytokine translation in immune cells. The altered expression of these cytokines is well-known to significantly influence immune activity within the tumor microenvironment. Bioinformatic analyses revealed that these miRNAs, along with their protein targets, are closely involved in oncogenic pathways, underscoring their potential as valuable tools in cancer therapeutics, diagnostics, and prognosis. Citation Format: Rupinder Kaur, Sandeep Bhoriwal, Pramod Kumar Gautam. MicroRNA cargo of extracellular vesicles of pancreatic cancer patients have immunoregulatory potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6679.