Ross A. Miller, Tara N. Miller, and Philip T. Cagle (2016) PD-1/PD-L1, Only a Piece of the Puzzle. Archives of Pathology & Laboratory Medicine: November 2016, Vol. 140, No. 11, pp. 1187-1188.
"PD-1/PD-L1 blockade undoubtedly provides an exciting therapeutic approach in malignancy. However, there is far more to immune-response damping than one receptor and one ligand. The control behind T-cell activation is a complex process requiring 2 distinct signaling pathways,13 and numerous molecules are involved. The first signal required for T-cell activation is antigen presentation via the major histocompatibility complex on antigen-presenting cells (APCs). The APCs interact with major histocompatibility complex via T-cell receptors. The second required signal is activation of CD28 (on the T cell). Ligands for CD28 include the B7 family of molecules.13 Some of the molecules in the B7/CD28 family include PD-1, PD-L1, PD-L2, CD80, and CTLA-4."