DCs are the most potent antigen-presenting cells. Tumor antigen-loaded DCs (DC-vaccines) that can activate and proliferate of specific cytotoxic T cells (CTLs) in draining lymph nodes (dLNs). DC vaccination has clinically relevant mechanisms of action with great potential for the systemic treatment of cancers. However, clinical trials have demonstrated relatively poor therapeutic efficacy. The limited success of DC therapy is often linked tumor immunosuppression (barriers to CTLs tumor infiltration) by the tumor microenvironment. To address these clinical gaps, we need to overcome tumor immunosuppression. IRE has been demonstrated to have a potential for the treatment of unresectable PDAC tumors in clinical settings due to cause the destruction of tumor microenvironment (by formation of nanopores in tumor cell membranes and reduction of tumor fibrosis) to increase tumor permeability; activated CTLs should more readily gain intra-tumoral access to enhance DC-based immunotherapy. In Aim 1, we advocate using novel intra-procedural MRI to quantitatively monitor antitumor effect of IRE, measure the alterations of tumor microenvironment and tumor CTLs (CDS•) infiltration in KPC mouse. In Aim 2, we will validate that IRE increases the therapeutic efficacy of DC vaccination for PDAC primary tumors and metastasis.
|Effective start/end date||6/1/20 → 5/31/21|
- SIR Foundation (AGMT 6/4/20)