CD274 and neoplasm: In-depth investigations have shown that replacing the ITIM and ITSM domains of PD-1 with ITAM or YINM motifs markedly enhances the degranulation and cytokine secretion capacities of NK-92 cell lines and primary NK cells against PD-L1-positive target cells, leading to stronger cytotoxic responses against CD138+PD-L1+ tumor samples [213].