CD274 and neoplasm: We postulate that, in addition to direct HER2 inhibition and ADCC, as is the case with trastuzumab, there are several novel mechanisms that may further contribute to the enhanced cytotoxicity of the BsAb: (1) the BsAb redirects T cells to the proximity of tumor cells and induces direct tumor cell killing most likely in an antigen-presentation-independent manner; (2) the BsAb can potentially activate T cells in the tumor microenvironment via PD1/PDL1 blockade, and (3) the BsAb is capable of further enhancing T cell cytotoxic activity by the formation of PD1 immunological synapses.