Fig. 9

Summary diagram of cytotoxicity mechanisms of intravesical instillation of NK cells and chemotherapy. (A) The mechanisms of different cytotoxicity of allogeneic NK cells against BCa and normal transitional cells. When encountering BCa cells, allogeneic NK cells were strongly activated through a mismatch of inhibitory KIR/MHC-I, activating MICA/B/NKG2D and B7H6/NKp30 signaling pathways. On the contrary, when encountering normal transitional cells, allogeneic NK cells were activated only through a mismatch of inhibitory KIR/MHC-I. (B) The mechanisms of different cytotoxicity of autologous NK cells against BCa and normal transitional cells. When encountering BCa cells, autologous NK cells were activated through relief of KIR/MHC-I inhibition due to loss of MHC-I on BCa cells, activating MICA/B/NKG2D and B7H6/NKp30 signaling pathways. On the contrary, when encountering normal transitional cells, autologous NK cells were inhibited through a match of the inhibitory KIR/MHC-I signaling pathway. (C) Chemotherapy exerts nonspecific cytotoxicity against BCa and normal cells by combining DNA in the nucleus. Abbreviations: BCa: bladder cancer; KIR: killer cell Ig-like receptor; MHC-I: major histocompatibility complex class I; MICA/B: MHC-I polypeptide-related sequences A and B; NKG2D: NK group 2 member D