Arlene Sharpe: Roles of the PD-1 pathway in controlling tolerance & tumor immunity

The immune response plays an important role in fighting cancer; however, the tumor environment is immunosuppressive and limits effective anti-tumor immunity. A new and promising strategy of tumor immunotherapy blocks pathways used by tumors to inhibit anti-tumor immunity. This inhibitory strategy is called checkpoint blockade. One key immunoinhibitory pathway that inhibits tumor specific immunity is the PD-1 co-inhibitory pathway. This pathway consists of the PD-1 receptor and its ligands PD-L1 (B7-H1) and PD-L2 (B7-DC). The PD-1 pathway plays critical roles in maintaining immune control, and is a key mediator of T cell dysfunction (“exhaustion”) in cancer and chronic infections. This pathway is a promising therapeutic target in cancer. The remarkable effects of PD-1 pathway blockade in cancer demonstrate the key role of this pathway in inhibiting anti-tumor immunity. However, there are multiple co-inhibitory pathways that that limit T cell function, and these have become targets for cancer therapy. This talk will discuss the multifaceted immunoregulatory roles of PD-1 and its ligands in controlling T cell activation, tolerance and exhaustion. The role of the PD-1 pathway in cancer as well as therapeutic strategies that combine PD-1 blockade with other therapies also will be discussed.