A multimodal immunotherapy with mRNA-induced cytokines (MIMIC), that is, oxaliplatin, anti-PD-1 and anti-CTLA-4 antibodies, and intratumoural administration of mRNA therapeutics encoding interferon-α and interleukin-12, was evaluated in this preclinical model.<h4>Findings</h4>The aggressive PDAC subtype exhibited a paucity of dendritic cells (DCs) and T cells, causing an immunosuppressive tumour microenvironment. Here, CTLA4 is linked to neoplasm.