|
|
自然杀伤细胞在急性髓细胞白血病治疗中的研究进展
|
Abstract:
急性髓细胞白血病(Acute Myeloid Leukemia, AML)是一种具有异质性遗传格局和复杂克隆进化特征的侵袭性血液系统恶性肿瘤。这种病在各个年龄段都有可能发生，而且随着年龄的增长，发病率也会越来越高。目前治疗AML面临着原发耐药和早期复发等挑战，因此需要寻找新的治疗方法。免疫治疗主要通过激活机体免疫反应来攻击肿瘤细胞，而不同于传统的化学疗法。造血干细胞移植也是依赖于供体免疫细胞对宿主白血球进行攻击和消灭以达到治疗白血病的目的。近年来，免疫治疗在AML治疗中受到越来越多的关注，以增强免疫应答为目的的新型抗肿瘤治疗策略的兴起，使自然杀伤(Nature Kill, NK)细胞成为备受关注的领域。NK细胞是一种可以直接识别抗原、非特异性地杀伤肿瘤细胞的机体固有免疫系统的细胞毒性淋巴细胞，是机体防御系统的第一道屏障。本文将对目前在急性髓系白血病治疗中NK细胞及其应用进展的机制探索进行总结。
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by a heterogeneous genetic profile and complex clonal evolution. AML can occur across all age groups, with an increasing incidence as age advances. Current treatment of AML is challenged by primary resistance and early relapse, underscoring the need for novel therapeutic strategies. Unlike traditional chemotherapy, immunotherapy targets tumor cells by activating the body’s immune response. Hematopoietic stem cell transplantation also relies on donor immune cells to attack and eradicate host leukemic cells, serving as a therapeutic approach for leukemia. In recent years, immunotherapy has garnered growing attention in the treatment of AML. The emergence of novel anti-tumor strategies aimed at enhancing immune responses has highlighted the importance of natural killer (NK) cells. NK cells are cytotoxic lymphocytes of the innate immune system, capable of directly recognizing antigens and non-specifically killing tumor cells, serving as the first line of defense in the body’s immune system. This review will summarize the current mechanistic insights and therapeutic advancements in the application of NK cells in the treatment of AML.
| [1] | 季晓君, 赵廷丽, 苗雷, 等. 急性髓系白血病的靶向治疗药物研发进展[J]. 肿瘤防治研究, 2023, 50(4): 413-421. |
| [2] | 金洁, 周一乐. 成人急性髓细胞白血病的诊断与治疗进展[J]. 临床血液学杂志, 2022, 35(5): 309-311, 317. |
| [3] | Döhner, H., Estey, E.H., Amadori, S., Appelbaum, F.R., Büchner, T., Burnett, A.K., et al. (2010) Diagnosis and Management of Acute Myeloid Leukemia in Adults: Recommendations from an International Expert Panel, on Behalf of the European Leukemianet. Blood, 115, 453-474. https://doi.org/10.1182/blood-2009-07-235358 |
| [4] | Papaemmanuil, E., Gerstung, M., Bullinger, L., Gaidzik, V.I., Paschka, P., Roberts, N.D., et al. (2016) Genomic Classification and Prognosis in Acute Myeloid Leukemia. New England Journal of Medicine, 374, 2209-2221. https://doi.org/10.1056/nejmoa1516192 |
| [5] | 王春键, 贾晋松, 江浩. NK细胞在急性髓细胞性白血病过继性免疫治疗中的应用及其进展[J]. 中国肿瘤生物治疗杂志, 2019, 26(6): 705-709. |
| [6] | Ramos, N., Mo, C., Karp, J. and Hourigan, C. (2015) Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia. Journal of Clinical Medicine, 4, 665-695. https://doi.org/10.3390/jcm4040665 |
| [7] | 中华医学会血液学分会. 急性髓系白血病(复发难治性)中国诊疗指南(2011年版) [J]. 中华血液学杂志, 2011, 32(12): 887-888. |
| [8] | Creutzig, U., van den Heuvel-Eibrink, M.M., Gibson, B., Dworzak, M.N., Adachi, S., de Bont, E., et al. (2012) Diagnosis and Management of Acute Myeloid Leukemia in Children and Adolescents: Recommendations from an International Expert Panel. Blood, 120, 3187-3205. https://doi.org/10.1182/blood-2012-03-362608 |
| [9] | Bose, P., Vachhani, P. and Cortes, J.E. (2017) Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Current Treatment Options in Oncology, 18, Article No. 17. https://doi.org/10.1007/s11864-017-0456-2 |
| [10] | Knorr, D.A., Bachanova, V., Verneris, M.R. and Miller, J.S. (2014) Clinical Utility of Natural Killer Cells in Cancer Therapy and Transplantation. Seminars in Immunology, 26, 161-172. https://doi.org/10.1016/j.smim.2014.02.002 |
| [11] | Arpinati, M. and Curti, A. (2013) Immunotherapy in Acute Myeloid Leukemia. Immunotherapy, 6, 95-106. https://doi.org/10.2217/imt.13.152 |
| [12] | Cooley, S., Parham, P. and Miller, J.S. (2018) Strategies to Activate NK Cells to Prevent Relapse and Induce Remission Following Hematopoietic Stem Cell Transplantation. Blood, 131, 1053-1062. https://doi.org/10.1182/blood-2017-08-752170 |
| [13] | Wu, Y., Tian, Z. and Wei, H. (2017) Developmental and Functional Control of Natural Killer Cells by Cytokines. Frontiers in Immunology, 8, Article 930. https://doi.org/10.3389/fimmu.2017.00930 |
| [14] | Mandal, A. and Viswanathan, C. (2015) Natural Killer Cells: In Health and Disease. Hematology/Oncology and Stem Cell Therapy, 8, 47-55. https://doi.org/10.1016/j.hemonc.2014.11.006 |
| [15] | Prager, I. and Watzl, C. (2019) Mechanisms of Natural Killer Cell-Mediated Cellular Cytotoxicity. Journal of Leukocyte Biology, 105, 1319-1329. https://doi.org/10.1002/jlb.mr0718-269r |
| [16] | Ochoa, M.C., Minute, L., Rodriguez, I., Garasa, S., Perez-Ruiz, E., Inogés, S., et al. (2017) Antibody-Dependent Cell Cytotoxicity: Immunotherapy Strategies Enhancing Effector NK Cells. Immunology & Cell Biology, 95, 347-355. https://doi.org/10.1038/icb.2017.6 |
| [17] | Farag, S.S., Fehniger, T.A., Ruggeri, L., Velardi, A. and Caligiuri, M.A. (2002) Natural Killer Cell Receptors: New Biology and Insights into the Graft-Versus-Leukemia Effect. Blood, 100, 1935-1947. https://doi.org/10.1182/blood-2002-02-0350 |
| [18] | Wu, J., Song, Y., Bakker, A.B.H., Bauer, S., Spies, T., Lanier, L.L., et al. (1999) An Activating Immunoreceptor Complex Formed by NKG2D and Dap10. Science, 285, 730-732. https://doi.org/10.1126/science.285.5428.730 |
| [19] | Biassoni, R., Cantoni, C., Marras, D., Giron-Michel, J., Falco, M., Moretta, L., et al. (2003) Human Natural Killer Cell Receptors: Insights into Their Molecular Function and Structure. Journal of Cellular and Molecular Medicine, 7, 376-387. https://doi.org/10.1111/j.1582-4934.2003.tb00240.x |
| [20] | Rincon-Orozco, B., Kunzmann, V., Wrobel, P., Kabelitz, D., Steinle, A. and Herrmann, T. (2005) Activation of Vγ9Vδ2 T Cells by NKG2D. The Journal of Immunology, 175, 2144-2151. https://doi.org/10.4049/jimmunol.175.4.2144 |
| [21] | Cosman, D., Müllberg, J., Sutherland, C.L., Chin, W., Armitage, R., Fanslow, W., et al. (2001) Ulbps, Novel MHC Class I-Related Molecules, Bind to CMV Glycoprotein UL16 and Stimulate NK Cytotoxicity through the NKG2D Receptor. Immunity, 14, 123-133. https://doi.org/10.1016/s1074-7613(01)00095-4 |
| [22] | Miller, J.S. and Lanier, L.L. (2019) Natural Killer Cells in Cancer Immunotherapy. Annual Review of Cancer Biology, 3, 77-103. https://doi.org/10.1146/annurev-cancerbio-030518-055653 |
| [23] | Orr, M.T. and Lanier, L.L. (2010) Natural Killer Cell Education and Tolerance. Cell, 142, 847-856. https://doi.org/10.1016/j.cell.2010.08.031 |
| [24] | Sandoval-Borrego, D., Moreno-Lafont, M.C., Vazquez-Sanchez, E.A., Gutierrez-Hoya, A., López-Santiago, R., Montiel-Cervantes, L.A., et al. (2016) Overexpression of CD158 and NKG2A Inhibitory Receptors and Underexpression of NKG2D and Nkp46 Activating Receptors on NK Cells in Acute Myeloid Leukemia. Archives of Medical Research, 47, 55-64. https://doi.org/10.1016/j.arcmed.2016.02.001 |
| [25] | Sanchez-Correa, B., Gayoso, I., Bergua, J.M., Casado, J.G., Morgado, S., Solana, R., et al. (2011) Decreased Expression of DNAM-1 on NK Cells from Acute Myeloid Leukemia Patients. Immunology & Cell Biology, 90, 109-115. https://doi.org/10.1038/icb.2011.15 |
| [26] | Fauriat, C., Just-Landi, S., Mallet, F., Arnoulet, C., Sainty, D., Olive, D., et al. (2006) Deficient Expression of NCR in NK Cells from Acute Myeloid Leukemia: Evolution during Leukemia Treatment and Impact of Leukemia Cells in NCRdull Phenotype Induction. Blood, 109, 323-330. https://doi.org/10.1182/blood-2005-08-027979 |
| [27] | Chretien, A., Devillier, R., Fauriat, C., Orlanducci, F., Harbi, S., Le Roy, A., et al. (2017) NKp46 Expression on NK Cells as a Prognostic and Predictive Biomarker for Response to Allo-SCT in Patients with AML. OncoImmunology, 6, e1307491. https://doi.org/10.1080/2162402x.2017.1307491 |
| [28] | Chretien, A., Fauriat, C., Orlanducci, F., Rey, J., Borg, G.B., Gautherot, E., et al. (2017) NKp30 Expression Is a Prognostic Immune Biomarker for Stratification of Patients with Intermediate-Risk Acute Myeloid Leukemia. Oncotarget, 8, 49548-49563. https://doi.org/10.18632/oncotarget.17747 |
| [29] | Nowbakht, P., Ionescu, M.S., Rohner, A., Kalberer, C.P., Rossy, E., Mori, L., et al. (2005) Ligands for Natural Killer Cell-Activating Receptors Are Expressed Upon the Maturation of Normal Myelomonocytic Cells but at Low Levels in Acute Myeloid Leukemias. Blood, 105, 3615-3622. https://doi.org/10.1182/blood-2004-07-2585 |
| [30] | Salih, H.R., Antropius, H., Gieseke, F., Lutz, S.Z., Kanz, L., Rammensee, H., et al. (2003) Functional Expression and Release of Ligands for the Activating Immunoreceptor NKG2D in Leukemia. Blood, 102, 1389-1396. https://doi.org/10.1182/blood-2003-01-0019 |
| [31] | Hilpert, J., Grosse-Hovest, L., Grünebach, F., Buechele, C., Nuebling, T., Raum, T., et al. (2012) Comprehensive Analysis of NKG2D Ligand Expression and Release in Leukemia: Implications for NKG2D-Mediated NK Cell Responses. The Journal of Immunology, 189, 1360-1371. https://doi.org/10.4049/jimmunol.1200796 |
| [32] | Rosenberg, S.A., Lotze, M.T., Muul, L.M., Leitman, S., Chang, A.E., Ettinghausen, S.E., et al. (1985) Observations on the Systemic Administration of Autologous Lymphokine-Activated Killer Cells and Recombinant Interleukin-2 to Patients with Metastatic Cancer. New England Journal of Medicine, 313, 1485-1492. https://doi.org/10.1056/nejm198512053132327 |
| [33] | Torelli, G.F., Guarini, A., Palmieri, G., Breccia, M., Vitale, A., Santoni, A., et al. (2002) Expansion of Cytotoxic Effectors with Lytic Activity against Autologous Blasts from Acute Myeloid Leukaemia Patients in Complete Haematological Remission. British Journal of Haematology, 116, 299-307. https://doi.org/10.1046/j.1365-2141.2002.03277.x |
| [34] | Sim, G.C., Martin-Orozco, N., Jin, L., Yang, Y., Wu, S., Washington, E., et al. (2013) IL-2 Therapy Promotes Suppressive ICOS+ Treg Expansion in Melanoma Patients. Journal of Clinical Investigation, 124, 99-110. https://doi.org/10.1172/jci46266 |
| [35] | Ruggeri, L., Mancusi, A., Capanni, M., Urbani, E., Carotti, A., Aloisi, T., et al. (2007) Donor Natural Killer Cell Allorecognition of Missing Self in Haploidentical Hematopoietic Transplantation for Acute Myeloid Leukemia: Challenging Its Predictive Value. Blood, 110, 433-440. https://doi.org/10.1182/blood-2006-07-038687 |
| [36] | Lee, D.A., Denman, C.J., Rondon, G., Woodworth, G., Chen, J., Fisher, T., et al. (2016) Haploidentical Natural Killer Cells Infused before Allogeneic Stem Cell Transplantation for Myeloid Malignancies: A Phase I Trial. Biology of Blood and Marrow Transplantation, 22, 1290-1298. https://doi.org/10.1016/j.bbmt.2016.04.009 |
| [37] | Miller, J.S., Soignier, Y., Panoskaltsis-Mortari, A., McNearney, S.A., Yun, G.H., Fautsch, S.K., et al. (2005) Successful Adoptive Transfer and in Vivo Expansion of Human Haploidentical NK Cells in Patients with Cancer. Blood, 105, 3051-3057. https://doi.org/10.1182/blood-2004-07-2974 |
| [38] | Bachanova, V., Cooley, S., Defor, T.E., Verneris, M.R., Zhang, B., McKenna, D.H., et al. (2014) Clearance of Acute Myeloid Leukemia by Haploidentical Natural Killer Cells Is Improved Using IL-2 Diphtheria Toxin Fusion Protein. Blood, 123, 3855-3863. https://doi.org/10.1182/blood-2013-10-532531 |
| [39] | Kildey, K., Francis, R.S., Hultin, S., Harfield, M., Giuliani, K., Law, B.M.P., et al. (2019) Specialized Roles of Human Natural Killer Cell Subsets in Kidney Transplant Rejection. Frontiers in Immunology, 10, Article 1877. https://doi.org/10.3389/fimmu.2019.01877 |
| [40] | Kerbauy, L., Ang, S., Liu, E., et al. (2017) Cord Blood NK Cells Engineered to Express a Humanized CD123-Targeted Chimeric Antigen Receptor (CAR) and IL-15 as Off-the-Shelf Therapy for Acute Myeloid Leukemia. Blood, 130, 4453. |
| [41] | Sellar, R. (2014) Preclinical Targeting of Human Acute Myeloid Leukemia and Myeloablation Using Chimeric Antigen Receptor-Modified T Cells. Blood, 123, 2343-54. |
| [42] | Liu, Y., Bewersdorf, J.P., Stahl, M. and Zeidan, A.M. (2019) Immunotherapy in Acute Myeloid Leukemia and Myelodysplastic Syndromes: The Dawn of a New Era? Blood Reviews, 34, 67-83. https://doi.org/10.1016/j.blre.2018.12.001 |
| [43] | Romain, G., Senyukov, V., Rey-Villamizar, N., Merouane, A., Kelton, W., Liadi, I., et al. (2014) Antibody FC Engineering Improves Frequency and Promotes Kinetic Boosting of Serial Killing Mediated by NK Cells. Blood, 124, 3241-3249. https://doi.org/10.1182/blood-2014-04-569061 |
| [44] | Hsu, J., Hodgins, J.J., Marathe, M., Nicolai, C.J., Bourgeois-Daigneault, M., Trevino, T.N., et al. (2018) Contribution of NK Cells to Immunotherapy Mediated by PD-1/PD-L1 Blockade. Journal of Clinical Investigation, 128, 4654-4668. https://doi.org/10.1172/jci99317 |
| [45] | Ghosh, A., Barba, P. and Perales, M. (2019) Checkpoint Inhibitors in AML: Are We There Yet? British Journal of Haematology, 188, 159-167. https://doi.org/10.1111/bjh.16358 |
| [46] | Gilliland, D.G. and Griffin, J.D. (2002) The Roles of FLT3 in Hematopoiesis and Leukemia. Blood, 100, 1532-1542. https://doi.org/10.1182/blood-2002-02-0492 |
| [47] | Cui, L., Liu, Y., Pang, Y., Qian, T., Quan, L., Cheng, Z., et al. (2019) Emerging Agents and Regimens for Treatment of Relapsed and Refractory Acute Myeloid Leukemia. Cancer Gene Therapy, 27, 1-14. https://doi.org/10.1038/s41417-019-0119-5 |
| [48] | Dhar, P. and Wu, J.D. (2018) NKG2D and Its Ligands in Cancer. Current Opinion in Immunology, 51, 55-61. https://doi.org/10.1016/j.coi.2018.02.004 |
| [49] | Aldoss, I., Yang, D., Aribi, A., Ali, H., Sandhu, K., Al Malki, M.M., et al. (2018) Efficacy of the Combination of Venetoclax and Hypomethylating Agents in Relapsed/Refractory Acute Myeloid Leukemia. Haematologica, 103, e404-e407. https://doi.org/10.3324/haematol.2018.188094 |
| [50] | Wu, H., Li, K., Pan, W., Guo, M., Qiu, D., He, Y., et al. (2022) Venetoclax Enhances NK Cell Killing Sensitivity of AML Cells through the NKG2D/NKG2DL Activation Pathway. International Immunopharmacology, 104, Article ID: 108497. https://doi.org/10.1016/j.intimp.2021.108497 |
| [51] | Vasu, S., He, S., Cheney, C., Gopalakrishnan, B., Mani, R., Lozanski, G., et al. (2016) Decitabine Enhances Anti-CD33 Monoclonal Antibody BI 836858—Mediated Natural Killer ADCC against AML Blasts. Blood, 127, 2879-2889. https://doi.org/10.1182/blood-2015-11-680546 |
| [52] | Cany, J., Roeven, M.W.H., Hoogstad-van Evert, J.S., Hobo, W., Maas, F., Franco Fernandez, R., et al. (2018) Decitabine Enhances Targeting of AML Cells by CD34+ Progenitor-Derived NK Cells in NOD/SCID/IL2RGnull Mice. Blood, 131, 202-214. https://doi.org/10.1182/blood-2017-06-790204 |
