Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Relevance of the KIR and HLA Class I Genes to the NK Cell Repertoire
2.1. KIR Genes
2.2. HLA Class I Genes
2.3. KIR/HLA Interactions and the KIR+ NK Cell Repertoire
3. Impacts of the KIR and HLA Class I Genes on the Antileukemic Effects of NK Cells in Patients with Acute Leukemia
3.1. Expression of HLA Class I Molecules on Leukemic Cells
3.2. Antileukemic NK Cell Function in Patients with Acute Leukemia
4. Selection of HSC Donors Based on the HLA and KIR Genes
4.1. Selection of HSC Donors Based on HLA Matching
4.2. KIR Models Used to Evaluate NK Cell Alloreactivity and Clinical Outcomes after Allogeneic HSCT
4.3. Reconstitution of NK Cells after T-Replete Haploidentical HSCT
5. NK-Cell-Based Immunotherapies Apart from HSCT
5.1. Immune Molecules for Boosting NK Cell Functions in Leukemic Patients
5.2. Adoptive NK Cell Immunotherapies
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Authors | N | AML 1 | HSCT | HLA | Source 2 | Depletion | Conditioning 3 | Outcome 4 |
---|---|---|---|---|---|---|---|---|
Hsu et al. [138] | 178 | 32% | Related | Matched | BM | T-cell-depleted | MAC | AML patients with missing KIR ligands (HLA-C or HLA-B ligands): ↗ OS, ↗ DFS, ↘ relapse |
Björklund et al. [101] | 105 | 77% | Related | Matched | PBSC (67%) and BM (33%) | T-replete | MAC (72%) and RIC (28%) | No benefit of missing KIR ligand on DFS, relapse, and aGvHD |
Hsu et al. [139] | 1770 | 13% | Unrelated | Matched (48%) and mismatched (52%) | unknown | T-replete | MAC | AML patients with missing KIR ligand: ↘ relapse in mismatched HSCT but no impact on matched HSCT |
Venstrom et al. [140] | 1277 | 100% | Unrelated | Matched (52%) and mismatched (48%) | BM (54%) and PBSC (46%) | T-replete (72%) and T-cell-depleted (28%) | MAC (85%) and RIC (15%) | Donor 2DS1+/C1+: ↘ TRM, ↘ relapse |
Gagne et al. [141] | 264 | 52% of acute leukemia | Unrelated | Matched (62%) and mismatched (38%) | BM | T-replete | TBI based (70%) | Donor KIR3DL1/S1+ and recipient Bw4+: ↗ OS, ↘ relapse for HLA-matched and HLA-mismatched HSCTs for malignant diseases |
Venstrom et al. [142] | 1087 | 28% | Unrelated | Matched (62%) and mismatched (38%) | BM (97%) | T-replete (80%) and T-cell-depleted (20%) | Unknown | Donor KIR3DS1+: ↘ TRM, ↘ aGvHD, no impact on relapse |
Cooley et al. [143] | 1409 | 77% | Unrelated | Matched (50%) and mismatched (50%) | BM (90%) and PBSC (10%) | T-replete | MAC | Donor CenBB or ≥ 2 KIR B gene content: ↗ DFS and ↘ relapse in matched and mismatched HSCTs.Donor TelBB: ↘ relapse |
Weisdorf et al. [144] | 2662 | 100% | Unrelated | Matched (89%) | BM (15%) and PBSC (85%) | Unknown | MAC (59%) and RIC (41%) | Donor KIR B haplotype: ↘ relapse only in RIC patients. Donor KIR B genes/ recipient C1+: ↘ relapse |
Boudreau et al. [148] | 1328 | 100% | Unrelated | Matched (53%) and mismatched (47%) | BM (54%) and PBSC (46%) | T-replete (92%) | MAC (84%) and RIC (16%) | Donor KIR3DL1/HLA-B subtype combinations linked to weak or non-inhibition: ↘ TRM, ↘ relapse. Distinct beneficial effect of donor KIR2DS1+/C1+ |
Ploeg et al. [149] | 604 | 100% | Unrelated | Matched (64%) and mismatched (36%) | BM (48%) and PBSC (52%) | T-replete (67%) and T-cell-depleted (33%) | MAC (85%) and RIC (15%) | Donor KIR3DL1+ and recipient HLA-A*24+: ↗ relapse |
Ruggeri et al. [135] | 92 | 62% | Related | Haplo-identical | unknown | T-cell depleted | Unknown | Donor/recipient KIR ligand mismatches in the GvH direction: no aGvHD and no relapse in AML patients |
Symons et al. [134] | 86 | 30% | Related | Haplo-identical | BM | T-replete | RIC, PTCy | Donor/recipient inh.KIR gene MM: ↗ OS, ↘ relapse, donor KIR B/recipient KIR AA ↗ OS, ↘ NRM |
Bastos et al. [161] | 33 | 30% | Related | Haplo-identical | unknown | T-replete | RIC (66%) and MAC (34%), PTCy | At least one donor/recipient inh KIR gene MM: ↗ EFS, ↘ relapse. No protective effect of donor B genotype |
Wanquet et al. [162] | 144 | 35% of myeloid diseases | Related | Haplo-identical | PBSC (63%) and BM (37%) | T-replete | RIC (87%), MAC (13%), PTCy | Donor/recipient KIR ligand MM in the GvH direction: ↘ relapse, ↗ PFS for patients with active disease but no beneficial effect for patients in complete remission |
Solomon et al. [163] | 208 | 34% | Related | Haplo-identical | PBSC and BM | T-replete | MAC (41%), RIC (59%), PTCy | Donor/recipient KIR ligand MM in the GvH direction or donor KIR2DS2+: ↗ OS, ↗ DFS, ↘ relapse. No impact on aGvHD |
Shimoni et al. [165] | 444 | 74% | Related | Haplo-identical | BM (53%) and PBSC (47%) | T-replete | MAC (55%) and RIC (45%), PTCy | Donor/recipient KIR ligand MM in the GvH direction: no impact on aGvHD, cGvHD and NRM. In AML patients grafted with PBSCs, ↗ relapse and ↘ OS |
Willem et al. [164] | 51 | 35% | Related | Haplo-identical | PBSC | T-replete | RIC, PTCy | Donor inh.KIR2D/recipient HLA-C MM: ↗ aGvHD, ↗ OS, ↗ DFS, ↘ relapse |
Dubreuil et al. [34] | 81 | 63% myeloid diseases | Related | Haplo-identical | PBSC | T-replete | RIC, PTCy | Donor CenAA: ↘ relapse only in patients with myeloid diseases |
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Dubreuil, L.; Chevallier, P.; Retière, C.; Gagne, K. Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients. Cancers 2021, 13, 3767. https://doi.org/10.3390/cancers13153767
Dubreuil L, Chevallier P, Retière C, Gagne K. Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients. Cancers. 2021; 13(15):3767. https://doi.org/10.3390/cancers13153767
Chicago/Turabian StyleDubreuil, Léa, Patrice Chevallier, Christelle Retière, and Katia Gagne. 2021. "Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients" Cancers 13, no. 15: 3767. https://doi.org/10.3390/cancers13153767