We study the molecular mechanisms that control T cell and NK cell function in the tumor microenvironment, with a particular focus on the pathways that constrain their effector function. We also study the mechanisms that enable tumor cells to resist an attack by T cells or NK cells. Our strategy integrates investigation of the immune system in human tumors with in-depth mechanistic investigation in model systems. We embrace the complexity of the human cancers and their interaction with the immune system as an opportunity to discover novel biology that opens new perspectives for cancer treatment. Of particular interest are strategies that are relevant for multiple cancer types. We hope to inspire advances in cancer treatment that harness the power of the immune system.