Tumour-microenvironment (TME)-driven immune suppression is well-recognized as a therapeutic target in pancreatic ductal adenocarcinoma (PDAC). Chibaya, DeMarco et al. investigated a combinatorial approach of delivering innate immune agonists and RAS pathway-targeted, senescence-inducing therapies to remodel the TME and improve PDAC drug response.

Moreover, combination treatment increased the total number of antigen-presenting dendritic cells, natural killer (NK) cells, CD4+ T cells and CD8+ T cells, as well as the percentage of activated and cytotoxic CD8+ T cells. In both KPC transplant mice and KPC GEMMs, this combinatorial treatment improved overall survival. More specifically, in KPC GEMMs this led to complete tumour response in 20% of mice.