Targeting the cAMP immune-inhibitory pathway in combinatorial cancer immunotherapy

One of the major obstacle for current cancer immunotherapy is the immunosuppressive tumor microenvironment allowing tumor cells to escape immunosurveillance and anti-tumor immunity. A recent significant finding is that cancer cell-derived PGE2 synthesis by cyclooxygenase 2 (COX-2) fuels cancer promoting inflammation and initiates the inhibitory PKA/cAMP pathway in effector T cells. Here, we will evaluate tumor development in transgenic mice expressing a peptide that block this immunomodulating cAMP signalling in combination with checkpoint inhibitors heterotopically implanted with syngeneic tumors. Our goal is thus to reveal potential synergistic effects of anti-tumor immune activity in combinatorial immune treatments in addition to gain mechanistic insight into the immune response..