CD274 and cancer: In 2004, PD-L1-expressing cancer cells were found to be significantly more resistant to T cell cytotoxicity by providing a protective molecular shield that inhibited their activities.87 It was also shown that PD-L1/PD-1-blocking antibodies could break this shield in cell cultures, restoring T cell cytotoxicity.4 The first evidence of the intrinsic signaling activities of PD-L1 independently of its function as a PD-1 engager was published in 2008.