The need for speed: how PD1-blockade only works if T cells are properly activated

Programmed death receptor 1 (PD1) has been identified as critical negative regulator of T cell activity (1). While PD1-mediated T cell inhibition is an important mechanism to prevent autoimmunity, cancer and chronic infectious diseases may usurp this regulation mechanism to drive immune suppression (2). In fact, the PD1-PD-L1 axis is one of the major axis used by a variety of cancer types to inhibit T cell responses and function (3). As a direct consequence, strategies interfering with PD1-signaling such as antibodies have entered the clinic and are approved in a number of indications (4). A remarkable aspect being that these so-called check point inhibitors also show significant activity in such clinical situations where any other therapy had previously failed (5).