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基于自然杀伤细胞的癌症免疫疗法的进展和前景
Natural Killer Cell-Based Immunotherapy for Cancer: Advances and Prospects
Natural killer (NK) cells are key innate immune cells that provide the first line of defense against viral infection and cancer. Although NK cells can discriminate between “self” and “non-self,” recognize abnormal cells, and eliminate transformed cells and malignancies in real time, tumors develop several strategies to escape from NK cell attack. These strategies include upregulating ligands for the inhibitory receptors of NK cells and producing soluble molecules or immunosuppressive factors. Various types of NK cells are currently being applied in clinical trials, including autologous or allogeneic NK cells, umbilical cord blood (UCB) or induced pluripotent stem cell (iPSC)-derived NK cells, memory-like NK cells, and NK cell line NK-92 cells, for the treatment of different types of tumors. Chimeric antigen receptors (CARs)-NK cells have recently shown great potential due to their redirect specificity and effective antitumor activity. In this review, we summarize the mechanisms of tumor escape from NK cell recognition, the current status and advanced progress of NK cell-based immunotherapy, ways of enhancing the antitumor capacity of NK cells in vivo, and major challenges for clinical practice in this field.
Natural killer cell / Immunotherapy / Cancer / Clinical trial / Chimeric antigen receptor
| [1] |
Cheng M., Chen Y., Xiao W., Sun R., Tian Z.. NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol. 2013; 10(3): 230-252.
|
| [2] |
Xiao T.S.. Innate immunity and inflammation. Cell Mol Immunol. 2017; 14(1): 1-3.
|
| [3] |
Long E.O., Kim H.S., Liu D., Peterson M.E., Rajagopalan S.. Controlling natural killer cell responses: integration of signals for activation and inhibition. Annu Rev Immunol. 2013; 31(1): 227-258.
|
| [4] |
Martinet L., Smyth M.J.. Balancing natural killer cell activation through paired receptors. Nat Rev Immunol. 2015; 15(4): 243-254.
|
| [5] |
De Pelsmaeker S., Romero N., Vitale M., Favoreel H.W.. Herpesvirus evasion of natural killer cells. J Virol. 2018; 92(11): e02105-17.
|
| [6] |
Sun C., Sun H.Y., Xiao W.H., Zhang C., Tian Z.G.. Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy. Acta Pharmacol Sin. 2015; 36(10): 1191-1199.
|
| [7] |
Berry R., Ng N., Saunders P.M., Vivian J.P., Lin J., Deuss F.A.,
|
| [8] |
Peng H., Jiang X., Chen Y., Sojka D.K., Wei H., Gao X.,
|
| [9] |
Li T., Wang J., Wang Y., Chen Y., Wei H., Sun R.,
|
| [10] |
Peng H., Sun R.. Liver-resident NK cells and their potential functions. Cell Mol Immunol. 2017; 14: 890-894.
|
| [11] |
Peng H., Wisse E., Tian Z.. Liver natural killer cells: subsets and roles in liver immunity. Cell Mol Immunol. 2016; 13(3): 328-336.
|
| [12] |
Marquardt N., Béziat V., Nyström S., Hengst J., Ivarsson M.A., Kekäläinen E.,
|
| [13] |
Hydes T., Noll A., Salinas-Riester G., Abuhilal M., Armstrong T., Hamady Z.,
|
| [14] |
Min-Oo G., Lanier L.L.. Cytomegalovirus generates long-lived antigen-specific NK cells with diminished bystander activation to heterologous infection. J Exp Med. 2014; 211(13): 2669-2680.
|
| [15] |
Foley B., Cooley S., Verneris M.R., Pitt M., Curtsinger J., Luo X.,
|
| [16] |
Liu L.L., Pfefferle A., Yi Sheng V.O., Björklund A.T., Béziat V., Goodridge J.P.,
|
| [17] |
Romee R., Schneider S.E., Leong J.W., Chase J.M., Keppel C.R., Sullivan R.P.,
|
| [18] |
Romee R., Rosario M., Berrien-Elliott M.M., Wagner J.A., Jewell B.A., Schappe T.,
|
| [19] |
Fang F., Xiao W., Tian Z.. NK cell-based immunotherapy for cancer. Semin Immunol. 2017; 31: 37-54.
|
| [20] |
Daher M., Rezvani K.. Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering. Curr Opin Immunol. 2018; 51: 146-153.
|
| [21] |
Maude S.L., Teachey D.T., Porter D.L., Grupp S.A.. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. 2015; 125(26): 4017-4023.
|
| [22] |
Rubnitz J.E., Inaba H., Ribeiro R.C., Pounds S., Rooney B., Bell T.,
|
| [23] |
Miller J.S., Soignier Y., Panoskaltsis-Mortari A., McNearney S.A., Yun G.H., Fautsch S.K.,
|
| [24] |
Shaffer B.C., Le Luduec J.B., Forlenza C., Jakubowski A.A., Perales M.A., Young J.W.,
|
| [25] |
Han K.P., Zhu X., Liu B., Jeng E., Kong L., Yovandich J.L.,
|
| [26] |
Xu W., Jones M., Liu B., Zhu X., Johnson C.B., Edwards A.C.,
|
| [27] |
Romee R., Cooley S., Berrien-Elliott M.M., Westervelt P., Verneris M.R., Wagner J.E.,
|
| [28] |
Rosario M., Liu B., Kong L., Collins L.I., Schneider S.E., Chen X.,
|
| [29] |
Wagner J.A., Rosario M., Romee R., Berrien-Elliott M.M., Schneider S.E., Leong J.W.,
|
| [30] |
Felices M., Chu S., Kodal B., Bendzick L., Ryan C., Lenvik A.J.,
|
| [31] |
Veuillen C., Aurran-Schleinitz T., Castellano R., Rey J., Mallet F., Orlanducci F.,
|
| [32] |
Reiners K.S., Kessler J., Sauer M., Rothe A., Hansen H.P., Reusch U.,
|
| [33] |
Paul S., Kulkarni N., Shilpi Lal G.. Intratumoral natural killer cells show reduced effector and cytolytic properties and control the differentiation of effector Th1 cells. OncoImmunology. 2016; 5(12): e1235106.
|
| [34] |
Ibrahim E.C., Guerra N., Lacombe M.J., Angevin E., Chouaib S., Carosella E.D.,
|
| [35] |
Polakova K., Bandzuchova E., Sabty F.A., Mistrik M., Demitrovicova L., Russ G.. Activation of HLA-G expression by 5-aza’-2-deoxycytidine in malignant hematopoietic cells isolated from leukemia patients. Neoplasma. 2009; 56(6): 514-520.
|
| [36] |
Wan R., Wang Z.W., Li H., Peng X.D., Liu G.Y., Ou J.M.,
|
| [37] |
Kailayangiri S., Altvater B., Spurny C., Jamitzky S., Schelhaas S., Jacobs A.H.,
|
| [38] |
Maki G., Hayes G.M., Naji A., Tyler T., Carosella E.D., Rouas-Freiss N.,
|
| [39] |
Chiu J., Ernst D.M., Keating A.. Acquired natural killer cell dysfunction in the tumor microenvironment of classic Hodgkin lymphoma. Front Immunol. 2018; 9: 267.
|
| [40] |
Reiners K.S., Topolar D., Henke A., Simhadri V.R., Kessler J., Sauer M.,
|
| [41] |
Binici J., Hartmann J., Herrmann J., Schreiber C., Beyer S., Güler G.,
|
| [42] |
Fernández-Messina L., Ashiru O., Boutet P., Agüera-González S., Skepper J.N., Reyburn H.T.,
|
| [43] |
Pogge von Strandmann E., Simhadri V.R., von Tresckow B., Sasse S., Reiners K.S., Hansen H.P.,
|
| [44] |
Zocchi M.R., Catellani S., Canevali P., Tavella S., Garuti A., Villaggio B.,
|
| [45] |
Ferrari de Andrade L., Tay R.E., Pan D., Luoma A.M., Ito Y., Badrinath S.,
|
| [46] |
Joyce J.A., Fearon D.T.. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015; 348(6230): 74-80.
|
| [47] |
Tang H., Qiao J., Fu Y.X.. Immunotherapy and tumor microenvironment. Cancer Lett. 2016; 370(1): 85-90.
|
| [48] |
Binnewies M., Roberts E.W., Kersten K., Chan V., Fearon D.F., Merad M.,
|
| [49] |
Mion F., Tonon S., Valeri V., Pucillo C.E.. Message in a bottle from the tumor microenvironment: tumor-educated DCs instruct B cells to participate in immunosuppression. Cell Mol Immunol. 2017; 14(9): 730-732.
|
| [50] |
Baginska J., Viry E., Paggetti J., Medves S., Berchem G., Moussay E.,
|
| [51] |
Pietra G., Manzini C., Rivara S., Vitale M., Cantoni C., Petretto A.,
|
| [52] |
Balsamo M., Scordamaglia F., Pietra G., Manzini C., Cantoni C., Boitano M.,
|
| [53] |
Li H., Han Y., Guo Q., Zhang M., Cao X.. Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-β1. J Immunol. 2009; 182(1): 240-249.
|
| [54] |
Cekic C., Day Y.J., Sag D., Linden J.. Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment. Cancer Res. 2014; 74(24): 7250-7259.
|
| [55] |
Bi J., Tian Z.. NK cell exhaustion. Front Immunol. 2017; 8: 760.
|
| [56] |
Sun C., Xu J., Huang Q., Huang M., Wen H., Zhang C.,
|
| [57] |
Zhang Q.F., Yin W.W., Xia Y., Yi Y.Y., He Q.F., Wang X.,
|
| [58] |
Krneta T., Gillgrass A., Chew M., Ashkar A.A.. The breast tumor microenvironment alters the phenotype and function of natural killer cells. Cell Mol Immunol. 2016; 13(5): 628-639.
|
| [59] |
Zhang Q., Bi J., Zheng X., Chen Y., Wang H., Wu W.,
|
| [60] |
Rosenberg S.A.. Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2. J Biol Response Mod. 1984; 3(5): 501-511.
|
| [61] |
Sakamoto N., Ishikawa T., Kokura S., Okayama T., Oka K., Ideno M.,
|
| [62] |
Ruggeri L., Capanni M., Urbani E., Perruccio K., Shlomchik W.D., Tosti A.,
|
| [63] |
Bachanova V., Burns L.J., McKenna D.H., Curtsinger J., Panoskaltsis-Mortari A., Lindgren B.R.,
|
| [64] |
Bachanova V., Sarhan D., DeFor T.E., Cooley S., Panoskaltsis-Mortari A., Blazar B.R.,
|
| [65] |
Björklund A.T., Carlsten M., Sohlberg E., Liu L.L., Clancy T., Karimi M.,
|
| [66] |
Curti A., Ruggeri L., D’Addio A., Bontadini A., Dan E., Motta M.R.,
|
| [67] |
Geller M.A., Cooley S., Judson P.L., Ghebre R., Carson L.F., Argenta P.A.,
|
| [68] |
Ishikawa T., Okayama T., Sakamoto N., Ideno M., Oka K., Enoki T.,
|
| [69] |
Lee D.A., Denman C.J., Rondon G., Woodworth G., Chen J., Fisher T.,
|
| [70] |
Adotevi O., Godet Y., Galaine J., Lakkis Z., Idirene I., Certoux J.M.,
|
| [71] |
Ciurea S.O., Schafer J.R., Bassett R., Denman C.J., Cao K., Willis D.,
|
| [72] |
Bachanova V., Cooley S., Defor T.E., Verneris M.R., Zhang B., McKenna D.H.,
|
| [73] |
Pillet A.H., Thèze J., Rose T.. Interleukin (IL)-2 and IL-15 have different effects on human natural killer lymphocytes. Hum Immunol. 2011; 72(11): 1013-1017.
|
| [74] |
Chen Y., Chen B., Yang T., Xiao W., Qian L., Ding Y.,
|
| [75] |
Spanholtz J., Tordoir M., Eissens D., Preijers F., van der Meer A., Joosten I.,
|
| [76] |
Knorr D.A., Ni Z., Hermanson D., Hexum M.K., Bendzick L., Cooper L.J.,
|
| [77] |
Herrera L., Salcedo J.M., Santos S., Vesga M.A., Borrego F., Eguizabal C.. OP9 feeder cells are superior to M2–10B4 cells for the generation of mature and functional natural killer cells from umbilical cord hematopoietic progenitors. Front Immunol. 2017; 8: 755.
|
| [78] |
Hermanson D.L., Bendzick L., Pribyl L., McCullar V., Vogel R.I., Miller J.S.,
|
| [79] |
Zeng J., Tang S.Y., Toh L.L., Wang S.. Generation of “off-the-shelf” natural killer cells from peripheral blood cell-derived induced pluripotent stem cells. Stem Cell Rep. 2017; 9(6): 1796-1812.
|
| [80] |
Xing D., Ramsay A.G., Gribben J.G., Decker W.K., Burks J.K., Munsell M.,
|
| [81] |
Veluchamy J.P., Lopez-Lastra S., Spanholtz J., Bohme F., Kok N., Heideman D.A.,
|
| [82] |
Ichise H., Nagano S., Maeda T., Miyazaki M., Miyazaki Y., Kojima H.,
|
| [83] |
Lehmann D., Spanholtz J., Sturtzel C., Tordoir M., Schlechta B., Groenewegen D.,
|
| [84] |
Veluchamy J.P., Heeren A.M., Spanholtz J., van Eendenburg J.D., Heideman D.A., Kenter G.G.,
|
| [85] |
Boudreau J.E., Hsu K.C.. Natural killer cell education in human health and disease. Curr Opin Immunol. 2018; 50: 102-111.
|
| [86] |
Boudreau J.E., Hsu K.C.. Natural killer cell education and the response to infection and cancer therapy: stay tuned. Trends Immunol. 2018; 39(3): 222-239.
|
| [87] |
Sarvaria A., Jawdat D., Madrigal J.A., Saudemont A.. Umbilical cord blood natural killer cells, their characteristics, and potential clinical applications. Front Immunol. 2017; 8: 329.
|
| [88] |
He Y., Tian Z.. NK cell education via nonclassical MHC and non-MHC ligands. Cell Mol Immunol. 2017; 14(4): 321-330.
|
| [89] |
Tam Y.K., Miyagawa B., Ho V.C., Klingemann H.G.. Immunotherapy of malignant melanoma in a SCID mouse model using the highly cytotoxic natural killer cell line NK-92. J Hematother. 1999; 8(3): 281-290.
|
| [90] |
Cheng M., Zhang J., Jiang W., Chen Y., Tian Z.. Natural killer cell lines in tumor immunotherapy. Front Med. 2012; 6(1): 56-66.
|
| [91] |
Cheng M., Ma J., Chen Y., Zhang J., Zhao W., Zhang J.,
|
| [92] |
Tonn T., Becker S., Esser R., Schwabe D., Seifried E.. Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92. J Hematother Stem Cell Res. 2001; 10(4): 535-544.
|
| [93] |
Arai S., Meagher R., Swearingen M., Myint H., Rich E., Martinson J.,
|
| [94] |
Tonn T., Schwabe D., Klingemann H.G., Becker S., Esser R., Koehl U.,
|
| [95] |
Boyiadzis M., Agha M., Redner R.L., Sehgal A., Im A., Hou J.Z.,
|
| [96] |
Gong J.H., Maki G., Klingemann H.G.. Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia. 1994; 8(4): 652-658.
|
| [97] |
Paul S., Lal G.. The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol. 2017; 8: 1124.
|
| [98] |
Ni J., Miller M., Stojanovic A., Garbi N., Cerwenka A.. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med. 2012; 209(13): 2351-2365.
|
| [99] |
Leong J.W., Chase J.M., Romee R., Schneider S.E., Sullivan R.P., Cooper M.A.,
|
| [100] |
Newhook N., Fudge N., Grant M.. NK cells generate memory-type responses to human cytomegalovirus-infected fibroblasts. Eur J Immunol. 2017; 47(6): 1032-1039.
|
| [101] |
Bigley A.B., Rezvani K., Shah N., Sekine T., Balneger N., Pistillo M.,
|
| [102] |
Liu L.L., Béziat V., Oei V.Y.S., Pfefferle A., Schaffer M., Lehmann S.,
|
| [103] |
Peng H., Tian Z.. Natural killer cell memory: progress and implications. Front Immunol. 2017; 8: 1143.
|
| [104] |
Oei V.Y.S., Siernicka M., Graczyk-Jarzynka A., Hoel H.J., Yang W., Palacios D.,
|
| [105] |
Peng H., Tian Z.. Tissue-resident natural killer cells in the livers. Sci China Life Sci. 2016; 59(12): 1218-1223.
|
| [106] |
Robinson M.W., Harmon C., O’Farrelly C.. Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol. 2016; 13(3): 267-276.
|
| [107] |
Jackson H.J., Rafiq S., Brentjens R.J.. Driving CAR T-cells forward. Nat Rev Clin Oncol. 2016; 13(6): 370-383.
|
| [108] |
Johnson L.A., June C.H.. Driving gene-engineered T cell immunotherapy of cancer. Cell Res. 2017; 27(1): 38-58.
|
| [109] |
Bedoya F., Frigault M.J., Maus M.V.. The flipside of the power of engineered T cells: observed and potential toxicities of genetically modified T cells as therapy. Mol Ther. 2017; 25(2): 314-320.
|
| [110] |
Hu Y., Tian Z.G., Zhang C.. Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. Acta Pharmacol Sin. 2018; 39(2): 167-176.
|
| [111] |
Han J., Chu J., Keung Chan W., Zhang J., Wang Y., Cohen J.B.,
|
| [112] |
Yu M., Luo H., Fan M., Wu X., Shi B., Di S.,
|
| [113] |
Shimasaki N., Fujisaki H., Cho D., Masselli M., Lockey T., Eldridge P.,
|
| [114] |
Oelsner S., Friede M.E., Zhang C., Wagner J., Badura S., Bader P.,
|
| [115] |
Müller T., Uherek C., Maki G., Chow K.U., Schimpf A., Klingemann H.G.,
|
| [116] |
Schirrmann T., Pecher G.. Specific targeting of CD33+ leukemia cells by a natural killer cell line modified with a chimeric receptor. Leuk Res. 2005; 29(3): 301-306.
|
| [117] |
Jiang H., Zhang W., Shang P., Zhang H., Fu W., Ye F.,
|
| [118] |
Chu J., Deng Y., Benson D.M., He S., Hughes T., Zhang J.,
|
| [119] |
Uherek C., Tonn T., Uherek B., Becker S., Schnierle B., Klingemann H.G.,
|
| [120] |
Töpfer K., Cartellieri M., Michen S., Wiedemuth R., Müller N., Lindemann D.,
|
| [121] |
Zhang C., Burger M.C., Jennewein L., Genßler S., Schönfeld K., Zeiner P.,
|
| [122] |
Zhang G., Liu R., Zhu X., Wang L., Ma J., Han H.,
|
| [123] |
Müller N., Michen S., Tietze S., Töpfer K., Schulte A., Lamszus K.,
|
| [124] |
Liu E., Tong Y., Dotti G., Shaim H., Savoldo B., Mukherjee M.,
|
| [125] |
Altvater B., Landmeier S., Pscherer S., Temme J., Schweer K., Kailayangiri S.,
|
| [126] |
Li Y., Hermanson D.L., Moriarity B.S., Kaufman D.S.. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell. 2018; 23(2): 181-192.
|
| [127] |
Hsu J., Hodgins J.J., Marathe M., Nicolai C.J., Bourgeois-Daigneault M.C., Trevino T.N.,
|
| [128] |
Pesce S., Greppi M., Tabellini G., Rampinelli F., Parolini S., Olive D.,
|
| [129] |
Dougall W.C., Kurtulus S., Smyth M.J., Anderson A.C.. TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol Rev. 2017; 276(1): 112-120.
|
| [130] |
Chew G.M., Fujita T., Webb G.M., Burwitz B.J., Wu H.L., Reed J.S.,
|
| [131] |
Chauvin J.M., Pagliano O., Fourcade J., Sun Z., Wang H., Sander C.,
|
| [132] |
Da Silva I.P., Gallois A., Jimenez-Baranda S., Khan S., Anderson A.C., Kuchroo V.K.,
|
| [133] |
Guillerey C., Huntington N.D., Smyth M.J.. Targeting natural killer cells in cancer immunotherapy. Nat Immunol. 2016; 17(9): 1025-1036.
|
This work was supported by grants from the National Natural Science Foundation of China (81788101, 81761128013, 81771686, 81472646, 91842305, 31390443, and 91542000) and the Chinese Academy of Science (XDB29030000).
Yuan Hu, Zhigang Tian, and Cai Zhang declare that they have no conflict of interest or financial conflicts to disclose.
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