Figure 6.
Both donor and host coexist all HLAs for donor 3 inhibitory KIRs associated with maximum responsiveness recovery of NK cells and least relapse following haplo-SCT. To allow for the evaluation of inhibitory KIRs and minimize interference from potential class I–recognizing activating KIRs and non-self HLA, we analyzed NK responsiveness from 9 donor-patients pairs of both of donor and host presenting all HLAs (Bw4C1C2) for haplotype A donor KIR presenting KIR3DL1, KIR2DL3, KIR2DL1 at the same time. The hierarchy of expression of CD107a (A) and IFN-γ (B) against K562 cells of NK subsets with expression of 3 (NKG2A−KIR2DL1+KIR2DL3+KIR3DL1+ NK), 2 (NKG2A−KIR2DL1+KIR2DL2/L3+ NK, NKG2A−KIR2DL1+KIR3DL1+ NK, or NKG2A−KIR2DL3+KIR3DL1+ NK), 1 (NKG2A−KIR2DL1+ NK, NKG2A-KIR2DL3+ NK, or NKG2A−KIR3DL1+ NK), or 0 (NKG2A−KIR−) inhibitory KIRs for self-HLA. To evaluate the predictive roles of the interaction of donor and host coexisting HLAs for donor inhibitory KIRs and clinical outcomes, in the second cohort, 276 AML or MDS patients who underwent haplo-SCT were subgrouped into the nsKIR group (n = 156), where both hosts and donors lacked HLA ligands for all 3 donor KIRs (ie, for donor C1C1, C2C2, C1C2, C1C1Bw4, or C2C2Bw4 and host C1C1, C2C2, C1C2, C1C1Bw4, or C2C2Bw4); the d-rsKIR group (n = 31), where donors and hosts encoded all HLA ligands for donor KIRs (ie, donor C1C2Bw4 to host C1C2Bw4); the dsKIR group (n = 33), where donors, but not hosts, encoded all HLA ligands for donor KIR (ie, for donor C1C2Bw4 and host C1C1, C2C2, C1C2, C1C1Bw4, or C2C2Bw4); and the rsKIR group (n = 55), where hosts, but not donors, encoded all HLA ligands for donor KIR (ie, for donor C1C1, C2C2, C1C2, C1C1Bw4, or C2C2Bw4 and host C1C2Bw4). The lowest relapse rate (C) was found in the d-rsKIR group (0%) compared with the rsKIR group (10.0% ± 4.9%, P = .115), dsKIR group (14.9% ± 7.0%, P = .039), or nsKIR group (18% ± 3.5%, P = .022). Therefore, higher LFS (D) and OS (E) were found in the d-rsKIR group compared with the nsKIR group (87.5% ± 5.8% vs 67.2% ± 3.8%, P = .046 and 87.5% ± 5.8% vs 68.1% ± 4.0%, P = .066).

Both donor and host coexist all HLAs for donor 3 inhibitory KIRs associated with maximum responsiveness recovery of NK cells and least relapse following haplo-SCT. To allow for the evaluation of inhibitory KIRs and minimize interference from potential class I–recognizing activating KIRs and non-self HLA, we analyzed NK responsiveness from 9 donor-patients pairs of both of donor and host presenting all HLAs (Bw4C1C2) for haplotype A donor KIR presenting KIR3DL1, KIR2DL3, KIR2DL1 at the same time. The hierarchy of expression of CD107a (A) and IFN-γ (B) against K562 cells of NK subsets with expression of 3 (NKG2A−KIR2DL1+KIR2DL3+KIR3DL1+ NK), 2 (NKG2A−KIR2DL1+KIR2DL2/L3+ NK, NKG2A−KIR2DL1+KIR3DL1+ NK, or NKG2A−KIR2DL3+KIR3DL1+ NK), 1 (NKG2A−KIR2DL1+ NK, NKG2A-KIR2DL3+ NK, or NKG2A−KIR3DL1+ NK), or 0 (NKG2A−KIR−) inhibitory KIRs for self-HLA. To evaluate the predictive roles of the interaction of donor and host coexisting HLAs for donor inhibitory KIRs and clinical outcomes, in the second cohort, 276 AML or MDS patients who underwent haplo-SCT were subgrouped into the nsKIR group (n = 156), where both hosts and donors lacked HLA ligands for all 3 donor KIRs (ie, for donor C1C1, C2C2, C1C2, C1C1Bw4, or C2C2Bw4 and host C1C1, C2C2, C1C2, C1C1Bw4, or C2C2Bw4); the d-rsKIR group (n = 31), where donors and hosts encoded all HLA ligands for donor KIRs (ie, donor C1C2Bw4 to host C1C2Bw4); the dsKIR group (n = 33), where donors, but not hosts, encoded all HLA ligands for donor KIR (ie, for donor C1C2Bw4 and host C1C1, C2C2, C1C2, C1C1Bw4, or C2C2Bw4); and the rsKIR group (n = 55), where hosts, but not donors, encoded all HLA ligands for donor KIR (ie, for donor C1C1, C2C2, C1C2, C1C1Bw4, or C2C2Bw4 and host C1C2Bw4). The lowest relapse rate (C) was found in the d-rsKIR group (0%) compared with the rsKIR group (10.0% ± 4.9%, P = .115), dsKIR group (14.9% ± 7.0%, P = .039), or nsKIR group (18% ± 3.5%, P = .022). Therefore, higher LFS (D) and OS (E) were found in the d-rsKIR group compared with the nsKIR group (87.5% ± 5.8% vs 67.2% ± 3.8%, P = .046 and 87.5% ± 5.8% vs 68.1% ± 4.0%, P = .066).

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