Current immunotherapy strategies have limited efficacy in treating pancreatic ductal adenocarcinoma (PDAC), a non-T cell inflamed tumor. Immune suppression of PDAC occurs due to the presence of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and M2 macrophages in the tumor microenvironment. While tremendous effort has focused on deciphering the biological pathways that regulate these immunosuppressive cells so that more effector T cells can infiltrate and kill cancer cells, little attention has been focused on the contribution of the multi-scale physical aberrations that are inherent in PDAC.
We believe that immunotherapy response and resistance in primary and metastatic sites are dependent on both the molecular and heterogeneous multi-scale physical properties of a specific PDAC tumor. In the CITO, we examine these phenomena, based on the notion that the efficacy of immunotherapy is limited by the spatial distribution of nutrients in the tumor microenvironment, as its disorganization restricts access of effector T cells to the cancer cells.