Immunotherapies targeting stimulatory pathways and beyond.

Co-stimulatory and co-inhibitory molecules play a critical role in T cell function. Tumor cells escape immune surveillance by promoting immunosuppression. Immunotherapy targeting inhibitory molecules like anti-CTLA-4 and anti-PD-1/PD-L1 were developed to overcome these immunosuppressive effects. These agents have demonstrated remarkable, durable responses in a small subset of patients. The other mechanisms for enhancing anti-tumor activities are to target the stimulatory pathways that are expressed on T cells or other immune cells. In this review, we summarize current phase I/II clinical trials evaluating novel immunotherapies targeting stimulatory pathways and outline their advantages, limitations, and future directions.