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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2023

Open Access 01-12-2023 | Lymphoma | Review

Novel target and treatment agents for natural killer/T-cell lymphoma

Authors: Xiao-Peng Tian, Yi Cao, Jun Cai, Yu-Chen Zhang, Qi-Hua Zou, Jin-Ni Wang, Yu Fang, Jia-Hui Wang, Song-Bin Guo, Qing-Qing Cai

Published in: Journal of Hematology & Oncology | Issue 1/2023

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Abstract

The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.
Literature
1.
Armitage JO, Gascoyne RD, Lunning MA, Cavalli F. Non-Hodgkin lymphoma. Lancet. 2017;390(10091):298–310.PubMedCrossRef
2.
3.
Yamaguchi M, Kita K, Miwa H, Nishii K, Oka K, Ohno T, et al. Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells. Cancer. 1995;76(11):2351–6.PubMedCrossRef
4.
NCCN Guidelines T-Cell Lymphomas Version 1. 2023.
5.
Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, et al. Phase I study of dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008;99(5):1016–20.PubMedCrossRef
6.
Qi S, Yahalom J, Hsu M, Chelius M, Lunning M, Moskowitz A, et al. Encouraging experience in the treatment of nasal type extra-nodal NK/T-cell lymphoma in a non-Asian population. Leuk Lymphoma. 2016;57(11):2575–83.PubMedPubMedCentralCrossRef
7.
Zhang Y, Ma S, Cai J, Yang Y, Jing H, Shuang Y, et al. Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: a multicenter study. Am J Hematol. 2021;96(11):1481–90.PubMedPubMedCentralCrossRef
8.
Wang X, Zhang L, Liu X, Li X, Li L, Fu X, et al. Efficacy and safety of a pegasparaginase-based chemotherapy regimen versus an l-asparaginase-based chemotherapy regimen for newly diagnosed advanced extranodal natural killer/T-cell lymphoma: a randomized clinical trial. JAMA Oncol. 2022;8(7):1035–41.PubMedPubMedCentralCrossRef
9.
10.
Lim SH, Hong JY, Lim ST, Hong H, Arnoud J, Zhao W, et al. Beyond first-line non-anthracycline-based chemotherapy for extranodal NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for patients after first relapse and progression of disease. Ann Oncol. 2017;28(9):2199–205.PubMedCrossRef
11.
12.
13.
14.
Wang L, Wang H, Li PF, Lu Y, Xia ZJ, Huang HQ, et al. CD38 expression predicts poor prognosis and might be a potential therapy target in extranodal NK/T cell lymphoma, nasal type. Ann Hematol. 2015;94(8):1381–8.PubMedCrossRef
15.
Li W, Liang L, Liao Q, Li Y, Zhou Y. CD38: an important regulator of T cell function. Biomed Pharmacother. 2022;153: 113395.PubMedCrossRef
16.
Huang H, Zhu J, Yao M, Kim TM, Yoon DH, Cho SG, et al. Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study. J Hematol Oncol. 2021;14(1):25.PubMedPubMedCentralCrossRef
17.
Chen L, Diao L, Yang Y, Yi X, Rodriguez BL, Li Y, et al. CD38-mediated Immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade. Cancer Discov. 2018;8(9):1156–75.PubMedPubMedCentralCrossRef
18.
19.
Wang GN, Zhao WG, Zhang XD, Jian XY, Zhang CL, Zhang MZ, et al. A retrospective study on the clinicopathological and molecular features of 22 cases of natural killer/T-cell lymphoma in children and adolescents. Sci Rep. 2022;12(1):7118.PubMedPubMedCentralCrossRef
20.
Kawamoto K, Miyoshi H, Suzuki T, Sasaki Y, Yamada K, Yanagida E, et al. Frequent expression of CD30 in extranodal NK/T-cell lymphoma: potential therapeutic target for anti-CD30 antibody-based therapy. Hematol Oncol. 2018;36(1):166–73.PubMedCrossRef
21.
Oishi N, Satou A, Miyaoka M, Kawashima I, Segawa T, Miyake K, et al. Genetic and immunohistochemical profiling of NK/T-cell lymphomas reveals prognostically relevant BCOR-MYC association. Blood Adv. 2023;7(1):178–89.PubMedCrossRef
22.
Kim SJ, Yoon DH, Kim JS, Kang HJ, Lee HW, Eom HS, et al. Efficacy of brentuximab vedotin in relapsed or refractory high-CD30-expressing non-Hodgkin lymphomas: results of a multicenter, open-labeled phase II trial. Cancer Res Treat. 2020;52(2):374–87.PubMedCrossRef
23.
Horwitz S, O’Connor OA, Pro B, Trümper L, Iyer S, Advani R, et al. The ECHELON-2 trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Ann Oncol. 2022;33(3):288–98.PubMedCrossRef
24.
Kim HK, Moon SM, Moon JH, Park JE, Byeon S, Kim WS. Complete remission in CD30-positive refractory extranodal NK/T-cell lymphoma with brentuximab vedotin. Blood Res. 2015;50(4):254–6.PubMedPubMedCentralCrossRef
25.
Poon LM, Kwong YL. Complete remission of refractory disseminated NK/T cell lymphoma with brentuximab vedotin and bendamustine. Ann Hematol. 2016;95(5):847–9.PubMedCrossRef
26.
Jiang L, Yuan CM, Hubacheck J, Janik JE, Wilson W, Morris JC, et al. Variable CD52 expression in mature T cell and NK cell malignancies: implications for alemtuzumab therapy. Br J Haematol. 2009;145(2):173–9.PubMedPubMedCentralCrossRef
27.
Chang ST, Lu CL, Chuang SS. CD52 expression in non-mycotic T- and NK/T-cell lymphomas. Leuk Lymphoma. 2007;48(1):117–21.PubMedCrossRef
28.
Poggio T, Duyster J, Illert AL. Current immunotherapeutic approaches in T cell non-Hodgkin lymphomas. Cancers (Basel). 2018;10:9.CrossRef
29.
Wulf GG, Altmann B, Ziepert M, D’Amore F, Held G, Greil R, et al. Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial. Leukemia. 2021;35(1):143–55.PubMedCrossRef
30.
Damoiseaux J. The IL-2 - IL-2 receptor pathway in health and disease: the role of the soluble IL-2 receptor. Clin Immunol. 2020;218: 108515.PubMedCrossRef
31.
Wang L, Liao DZ, Zhang J, Xia ZJ, Peng XW, Lu Y. Clinical significance of serum soluble interleukin-2 receptor-α in extranodal natural killer/T-cell lymphoma (ENKTL): a predictive biomarker for treatment efficacy and valuable prognostic factor. Med Oncol. 2013;30(4):723.PubMedCrossRef
32.
Wang L, Bi XW, Zhu YJ, He YZ, Lai QY, Xia ZJ, et al. IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma. Cancer Commun (Lond). 2018;38(1):62.PubMedCrossRef
33.
Laurence AD. Location, movement and survival: the role of chemokines in haematopoiesis and malignancy. Br J Haematol. 2006;132(3):255–67.PubMedCrossRef
34.
Kumai T, Nagato T, Kobayashi H, Komabayashi Y, Ueda S, Kishibe K, et al. CCL17 and CCL22/CCR4 signaling is a strong candidate for novel targeted therapy against nasal natural killer/T-cell lymphoma. Cancer Immunol Immunother. 2015;64(6):697–705.PubMedPubMedCentralCrossRef
35.
Kanazawa T, Hiramatsu Y, Iwata S, Siddiquey M, Sato Y, Suzuki M, et al. Anti-CCR4 monoclonal antibody mogamulizumab for the treatment of EBV-associated T- and NK-cell lymphoproliferative diseases. Clin Cancer Res. 2014;20(19):5075–84.PubMedCrossRef
36.
Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(9):1192–204.PubMedCrossRef
37.
Karnell JL, Rieder SA, Ettinger R, Kolbeck R. Targeting the CD40-CD40L pathway in autoimmune diseases: humoral immunity and beyond. Adv Drug Deliv Rev. 2019;141:92–103.PubMedCrossRef
38.
Imadome K, Shimizu N, Arai A, Miura O, Watanabe K, Nakamura H, et al. Coexpression of CD40 and CD40 ligand in Epstein-Barr virus-infected T and NK cells and their role in cell survival. J Infect Dis. 2005;192(8):1340–8.PubMedCrossRef
39.
Fayad L, Ansell SM, Advani R, Coiffier B, Stuart R, Bartlett NL, et al. Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial. Leuk Lymphoma. 2015;56(9):2569–78.PubMedCrossRef
40.
Zhao B, Li H, Xia Y, Wang Y, Wang Y, Shi Y, et al. Immune checkpoint of B7–H3 in cancer: from immunology to clinical immunotherapy. J Hematol Oncol. 2022;15(1):153.PubMedPubMedCentralCrossRef
41.
Zheng M, Yu L, Hu J, Zhang Z, Wang H, Lu D, et al. Efficacy of B7-H3-redirected BiTE and CAR-T immunotherapies against extranodal nasal natural killer/T cell lymphoma. Transl Oncol. 2020;13(5): 100770.PubMedPubMedCentralCrossRef
42.
43.
Yoshino K, Kishibe K, Nagato T, Ueda S, Komabayashi Y, Takahara M, et al. Expression of CD70 in nasal natural killer/T cell lymphoma cell lines and patients; its role for cell proliferation through binding to soluble CD27. Br J Haematol. 2013;160(3):331–42.PubMedCrossRef
44.
Yoshimori M, Imadome K, Komatsu H, Wang L, Saitoh Y, Yamaoka S, et al. CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals. PLoS ONE. 2014;9(11): e112564.PubMedPubMedCentralCrossRef
45.
Somekh I, Thian M, Medgyesi D, Gülez N, Magg T, Gallón Duque A, et al. CD137 deficiency causes immune dysregulation with predisposition to lymphomagenesis. Blood. 2019;134(18):1510–6.PubMedPubMedCentralCrossRef
46.
Rodriguez R, Fournier B, Cordeiro DJ, Winter S, Izawa K, Martin E, et al. Concomitant PIK3CD and TNFRSF9 deficiencies cause chronic active Epstein-Barr virus infection of T cells. J Exp Med. 2019;216(12):2800–18.PubMedPubMedCentralCrossRef
47.
48.
Kim WY, Jung HY, Nam SJ, Kim TM, Heo DS, Kim CW, et al. Expression of programmed cell death ligand 1 (PD-L1) in advanced stage EBV-associated extranodal NK/T cell lymphoma is associated with better prognosis. Virchows Arch. 2016;469(5):581–90.PubMedCrossRef
49.
Jo JC, Kim M, Choi Y, Kim HJ, Kim JE, Chae SW, et al. Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type. Ann Hematol. 2017;96(1):25–31.PubMedCrossRef
50.
Feng Y, Feng X, Jing C, Yu X, Zheng Y, Xu C. The expression and clinical significance of programmed cell death receptor 1 and its ligand in tumor tissues of patients with extranodal nasal NK/T cell lymphoma. Sci Rep. 2022;12(1):36.PubMedPubMedCentralCrossRef
51.
Nagato T, Ohkuri T, Ohara K, Hirata Y, Kishibe K, Komabayashi Y, et al. Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Cancer Immunol Immunother. 2017;66(7):877–90.PubMedCrossRef
52.
Laurent C, Fabiani B, Do C, Tchernonog E, Cartron G, Gravelle P, et al. Immune-checkpoint expression in Epstein-Barr virus positive and negative plasmablastic lymphoma: a clinical and pathological study in 82 patients. Haematologica. 2016;101(8):976–84.PubMedPubMedCentralCrossRef
53.
Fang W, Hong S, Chen N, He X, Zhan J, Qin T, et al. PD-L1 is remarkably over-expressed in EBV-associated pulmonary lymphoepithelioma-like carcinoma and related to poor disease-free survival. Oncotarget. 2015;6(32):33019–32.PubMedPubMedCentralCrossRef
54.
Bi XW, Wang H, Zhang WW, Wang JH, Liu WJ, Xia ZJ, et al. PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma. J Hematol Oncol. 2016;9(1):109.PubMedPubMedCentralCrossRef
55.
Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017;129(17):2437–42.PubMedCrossRef
56.
57.
Chan TSY, Li J, Loong F, Khong PL, Tse E, Kwong YL. PD1 blockade with low-dose nivolumab in NK/T cell lymphoma failing l-asparaginase: efficacy and safety. Ann Hematol. 2018;97(1):193–6.PubMedCrossRef
58.
Tao R, Fan L, Song Y, Hu Y, Zhang W, Wang Y, et al. Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4). Signal Transduct Target Ther. 2021;6(1):365.PubMedPubMedCentralCrossRef
59.
Cai J, Liu P, Huang H, Li Y, Ma S, Zhou H, et al. Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma. Signal Transduct Target Ther. 2020;5(1):289.PubMedPubMedCentralCrossRef
60.
Kim SJ, Lim JQ, Laurensia Y, Cho J, Yoon SE, Lee JY, et al. Avelumab for the treatment of relapsed or refractory extranodal NK/T-cell lymphoma: an open-label phase 2 study. Blood. 2020;136(24):2754–63.PubMedCrossRef
61.
Huang H, Tao R, Yang Y, Cen H, Zhou H, Guo Y, et al. GEMSTONE-201: preplanned primary analysis of a multicenter, single-arm, phase 2 study of sugemalimab (suge) in patients (pts) with relapsed or refractory extranodal natural killer/T cell lymphoma (R/R ENKTL). J Clin Oncol. 2022;40(16):7501–7501.CrossRef
62.
Huang H, Tao R, Hao S, Yang Y, Cen H, Zhou H, et al. Sugemalimab monotherapy for patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (GEMSTONE-201): results from a single-arm, multicenter, phase II study. J Clin Oncol. 2023;41:3032–41.PubMedCrossRef
63.
Song TL, Nairismägi ML, Laurensia Y, Lim JQ, Tan J, Li ZM, et al. Oncogenic activation of the STAT3 pathway drives PD-L1 expression in natural killer/T-cell lymphoma. Blood. 2018;132(11):1146–58.PubMedPubMedCentralCrossRef
64.
Liao Z, Lv X, Liu S, He Z, Chen S, Wang L, et al. Different aberrant expression pattern of immune checkpoint receptors in patients with PTCL and NK/T-CL. Asia Pac J Clin Oncol. 2018;14(5):e252–8.PubMedCrossRef
65.
Lin R, Li X, Wu S, Qian S, Hou H, Dong M, et al. Suppression of latent transforming growth factor-β (TGF-β)-binding protein 1 (LTBP1) inhibits natural killer/ T cell lymphoma progression by inactivating the TGF-β/Smad and p38(MAPK) pathways. Exp Cell Res. 2021;407(1): 112790.PubMedCrossRef
66.
Dunmire SK, Verghese PS, Balfour HH Jr. Primary Epstein-Barr virus infection. J Clin Virol. 2018;102:84–92.PubMedCrossRef
67.
Fox CP, Haigh TA, Taylor GS, Long HM, Lee SP, Shannon-Lowe C, et al. A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK- and T-cell lymphoproliferative disease encodes a target for cellular immunotherapy. Blood. 2010;116(19):3695–704.PubMedPubMedCentralCrossRef
68.
Harabuchi Y, Imai S, Wakashima J, Hirao M, Kataura A, Osato T, et al. Nasal T-cell lymphoma causally associated with Epstein-Barr virus: clinicopathologic, phenotypic, and genotypic studies. Cancer. 1996;77(10):2137–49.PubMedCrossRef
69.
Haverkos BM, Coleman C, Gru AA, Pan Z, Brammer J, Rochford R, et al. Emerging insights on the pathogenesis and treatment of extranodal NK/T cell lymphomas (ENKTL). Discov Med. 2017;23(126):189–99.PubMedPubMedCentral
70.
Sun L, Zhao Y, Shi H, Ma C, Wei L. LMP1 promotes nasal NK/T-cell lymphoma cell function by eIF4E via NF-κB pathway. Oncol Rep. 2015;34(6):3264–71.PubMedCrossRef
71.
Bollard CM, Gottschalk S, Torrano V, Diouf O, Ku S, Hazrat Y, et al. Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol. 2014;32(8):798–808.PubMedCrossRef
72.
Cho SG, Kim N, Sohn HJ, Lee SK, Oh ST, Lee HJ, et al. Long-term outcome of extranodal NK/T cell lymphoma patients treated with postremission therapy using EBV LMP1 and LMP2a-specific CTLs. Mol Ther. 2015;23(8):1401–9.PubMedPubMedCentralCrossRef
73.
Kim WS, Oki Y, Kim SJ, Yoon SE, Ardeshna KM, Lin Y, et al. Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study. Ann Hematol. 2021;100(10):2529–39.PubMedCrossRef
74.
Wu H, Zhao C, Gu K, Jiao Y, Hao J, Sun G. Thalidomide plus chemotherapy exhibit enhanced efficacy in the clinical treatment of T-cell non-Hodgkin’s lymphoma: a prospective study of 46 cases. Mol Clin Oncol. 2014;2(5):695–700.PubMedPubMedCentralCrossRef
75.
Wang L, Wang ZH, Chen XQ, Wang KF, Huang HQ, Xia ZJ. First-line combination of GELOX followed by radiation therapy for patients with stage IE/IIE ENKTL: an updated analysis with long-term follow-up. Oncol Lett. 2015;10(2):1036–40.PubMedPubMedCentralCrossRef
76.
Zhang L, Liu X, Wang X, Chang Y, Fu X, Li X, et al. Anti-PD-1-antibody (Tislelizumab) combined with deacetylase inhibitor (Chidamide), lenalidomide and etoposide for the treatment of refractory/relapsed extranodal natural killer/T cell lymphoma, Nasal. European Hematology Association 2022, Poster Abstract P1240.
77.
Westin JR, Kersten MJ, Salles G, Abramson JS, Schuster SJ, Locke FL, et al. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Am J Hematol. 2021;96(10):1295–312.PubMedPubMedCentralCrossRef
78.
79.
Kontos F, Michelakos T, Kurokawa T, Sadagopan A, Schwab JH, Ferrone CR, et al. B7–H3: an attractive target for antibody-based immunotherapy. Clin Cancer Res. 2021;27(5):1227–35.PubMedCrossRef
80.
81.
Xiong J, Cui BW, Wang N, Dai YT, Zhang H, Wang CF, et al. Genomic and transcriptomic characterization of natural killer T cell lymphoma. Cancer Cell. 2020;37(3):403-419.e406.PubMedCrossRef
82.
83.
Awasthi N, Liongue C, Ward AC. STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer. J Hematol Oncol. 2021;14(1):198.PubMedPubMedCentralCrossRef
84.
Bouchekioua A, Scourzic L, de Wever O, Zhang Y, Cervera P, Aline-Fardin A, et al. JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma. Leukemia. 2014;28(2):338–48.PubMedCrossRef
85.
Koo GC, Tan SY, Tang T, Poon SL, Allen GE, Tan L, et al. Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discov. 2012;2(7):591–7.PubMedCrossRef
86.
Geng L, Li X, Zhou X, Fang X, Yuan D, Wang X. WP1066 exhibits antitumor efficacy in nasal-type natural killer/T-cell lymphoma cells through downregulation of the STAT3 signaling pathway. Oncol Rep. 2016;36(5):2868–74.PubMedCrossRef
87.
Liu J, Liang L, Li D, Nong L, Zheng Y, Huang S, et al. JAK3/STAT3 oncogenic pathway and PRDM1 expression stratify clinicopathologic features of extranodal NK/T-cell lymphoma, nasal type. Oncol Rep. 2019;41(6):3219–32.PubMedPubMedCentral
88.
Sim SH, Kim S, Kim TM, Jeon YK, Nam SJ, Ahn YO, et al. Novel JAK3-activating mutations in extranodal NK/T-cell lymphoma, Nasal type. Am J Pathol. 2017;187(5):980–6.PubMedCrossRef
89.
Zhu J, Song Y, Zhao W, Zhou K, Wu J, Zhang H, et al. Golidocitinib in treating refractory or relapsed peripheral T-cell lymphoma: primary analysis of the multinational pivotal study results (JACKPOT8). J Clin Oncol. 2023;41(16):7503–7503.
90.
Jost PJ, Ruland J. Aberrant NF-kappaB signaling in lymphoma: mechanisms, consequences, and therapeutic implications. Blood. 2007;109(7):2700–7.PubMedCrossRef
91.
Huang Y, de Reyniès A, de Leval L, Ghazi B, Martin-Garcia N, Travert M, et al. Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Blood. 2010;115(6):1226–37.PubMedPubMedCentralCrossRef
92.
Liu X, Wang B, Ma X, Guo Y. NF-kappaB activation through the alternative pathway correlates with chemoresistance and poor survival in extranodal NK/T-cell lymphoma, nasal type. Jpn J Clin Oncol. 2009;39(7):418–24.PubMedCrossRef
93.
Ng SB, Selvarajan V, Huang G, Zhou J, Feldman AL, Law M, et al. Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T cell lymphoma revealed by gene expression profiling. J Pathol. 2011;223(4):496–510.PubMedCrossRef
94.
Iwata S, Yano S, Ito Y, Ushijima Y, Gotoh K, Kawada J, et al. Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein-Barr virus infection. Int J Cancer. 2011;129(9):2263–73.PubMedCrossRef
95.
Tang T, Tay K, Tao M, Quek RHH, Farid M, Lim ST. A Phase II study of bortezomib-GIFOX (Gemcitabine, Ifosfamide, Oxaliplatin) in patients with newly diagnosed natural-killer/T-cell lymphoma. Blood. 2016;128(22):5353–5353.CrossRef
96.
Granato M, Romeo MA, Tiano MS, Santarelli R, Gonnella R, Gilardini Montani MS, et al. Bortezomib promotes KHSV and EBV lytic cycle by activating JNK and autophagy. Sci Rep. 2017;7(1):13052.PubMedPubMedCentralCrossRef
97.
Ganjoo K, Hong F, Horning SJ, Gascoyne RD, Natkunam Y, Swinnen LJ, et al. Bevacizumab and cyclosphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms: an Eastern Cooperative Oncology Group study (E2404). Leuk Lymphoma. 2014;55(4):768–72.PubMedCrossRef
98.
99.
Li J, Chen P, Liu W, Xia Z, Shi F, Zhong M. Expression and significance of Ku80 and PDGFR-α in nasal NK/T-cell lymphoma. Pathol Res Pract. 2016;212(3):204–9.PubMedCrossRef
100.
Lu L, Fu X, Li Z, Qiu Y, Li W, Zhou Z, et al. Platelet-derived growth factor receptor alpha (PDGFRα) is overexpressed in NK/T-cell lymphoma and mediates cell survival. Biochem Biophys Res Commun. 2018;504(2):525–31.PubMedCrossRef
101.
102.
Huang D, Song TL, Nairismägi ML, Laurensia Y, Pang WL, Zhe DCM, et al. Evaluation of the PIK3 pathway in peripheral T-cell lymphoma and NK/T-cell lymphoma. Br J Haematol. 2020;189(4):731–44.PubMedPubMedCentralCrossRef
103.
Kawada J, Ito Y, Iwata S, Suzuki M, Kawano Y, Kanazawa T, et al. mTOR inhibitors induce cell-cycle arrest and inhibit tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells. Clin Cancer Res. 2014;20(21):5412–22.PubMedCrossRef
104.
105.
Trkulja KL, Manji F, Kuruvilla J, Laister RC. Nuclear export in non-Hodgkin lymphoma and implications for targeted XPO1 inhibitors. Biomolecules. 2023;13:1.CrossRef
106.
Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7(7):e511–22.PubMedCrossRef
107.
Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, Yee AJ, Huff CA, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727–38.PubMedCrossRef
108.
Tang T, Martin P, Somasundaram N, Lim C, Tao M, Poon E, et al. Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma. Haematologica. 2021;106(12):3170–5.PubMedCrossRef
109.
Huang H, Gao Y, Zhang H, Zhou K, Wu J, Cai Z, et al. XPO1 inhibitor (ATG-010) plus GemOx regimen for heavily pretreated patients with relapsed or refractory (R/R) T and NK-cell lymphoma: updates of the phase Ib touch study. Blood. 2022;140(Supplement 1):6554–5.CrossRef
110.
111.
112.
Iqbal J, Weisenburger DD, Chowdhury A, Tsai MY, Srivastava G, Greiner TC, et al. Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro. Leukemia. 2011;25(2):348–58.PubMedCrossRef
113.
Berglund A, Putney RM, Hamaidi I, Kim S. Epigenetic dysregulation of immune-related pathways in cancer: bioinformatics tools and visualization. Exp Mol Med. 2021;53(5):761–71.PubMedPubMedCentralCrossRef
114.
Zhang P, Zhang M. Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma. Clin Epigen. 2020;12(1):169.CrossRef
115.
Dobashi A, Tsuyama N, Asaka R, Togashi Y, Ueda K, Sakata S, et al. Frequent BCOR aberrations in extranodal NK/T-Cell lymphoma, nasal type. Genes Chromosomes Cancer. 2016;55(5):460–71.PubMedCrossRef
116.
Lee S, Park HY, Kang SY, Kim SJ, Hwang J, Lee S, et al. Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type. Oncotarget. 2015;6(19):17764–76.PubMedPubMedCentralCrossRef
117.
118.
Yan G, Huang H-Q, Li P, Bing B, Xiaoxiao W, Qixiang R, et al. Chidamide, oral subtype-selective histone deacetylase inhibitor (HDACI) monotherapy was effective on the patients with relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma. Blood. 2017;130(Supplement 1):2797–2797.
119.
Shi Y, Jia B, Xu W, Li W, Liu T, Liu P, et al. Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China. J Hematol Oncol. 2017;10(1):69.PubMedPubMedCentralCrossRef
120.
Huang H, Gao Y, Wang X, Bai B, Zhang L, Xiao Y, et al. Sintilimab plus chidamide for relapsed/refractory (R/R) extranodal NK/T cell lymphoma (ENKTL): a prospective, multicenter, single-arm, phase Ib/II trial (SCENT). Hematol Oncol. 2021;39:S2.CrossRef
121.
Tan D, Diong CP, Loh Y, Goh YT. Histone deacetylase (HDAC) inhibitors when combined with a proteasome inhibitor are safe and effective in patients with extranodal natural killer/T-cell lymphoma (ENKTL). Ann Oncol. 2016;27(9):1811–2.PubMedCrossRef
122.
Kim SJ, Kim JH, Ki CS, Ko YH, Kim JS, Kim WS. Epstein-Barr virus reactivation in extranodal natural killer/T-cell lymphoma patients: a previously unrecognized serious adverse event in a pilot study with romidepsin. Ann Oncol. 2016;27(3):508–13.PubMedCrossRef
123.
Tsai PF, Lin SJ, Weng PL, Tsai SC, Lin JH, Chou YC, et al. Interplay between PKCδ and Sp1 on histone deacetylase inhibitor-mediated Epstein-Barr virus reactivation. J Virol. 2011;85(5):2373–85.PubMedCrossRef
124.
Küçük C, Hu X, Jiang B, Klinkebiel D, Geng H, Gong Q, et al. Global promoter methylation analysis reveals novel candidate tumor suppressor genes in natural killer cell lymphoma. Clin Cancer Res. 2015;21(7):1699–711.PubMedPubMedCentralCrossRef
125.
Liu W, Yang Y, Qi S, Wang Y, He X, Zhang L, et al. Treatment, survival, and prognosis of advanced-stage natural killer/T-cell lymphoma: an analysis from the China Lymphoma Collaborative Group. Front Oncol. 2020;10: 583050.PubMedCrossRef
126.
Cai Q, Liu P, Xia Y, Cai J, Huang H, Li Z, et al. Sintilimab plus P-gemox (Pegaspargase, Gemcitabine and Oxaliplatin) regimen for newly-diagnosed advanced, extranodal natural killer/T cell lymphoma, Nasal type: a multicenter, phase 2 cohort of the open-label spirit study. Blood. 2022;140(Supplement 1):2299–301.CrossRef
127.
Sun P, Li Y, Li C, Ren K, Wang Y, Yang H, et al. A phase II study of sintilimab, anlotinib, and pegaspargase sandwiched with radiotherapy as first-line therapy in patients with newly diagnosed, stage I–II extranodal natural-killer/T-cell lymphoma. Am J Hematol. 2023;98(7):1043–51.PubMedCrossRef
128.
Bachy E, Savage KJ, Huang H, Kwong Y-L, Gritti G, Zhang Q, et al. Tislelizumab, a PD-1 inhibitor for relapsed/refractory mature T/NK-cell neoplasms: Results from a phase 2 study. J Clin Oncol. 2022;40(16):7552–7552.CrossRef
Metadata
Title
Novel target and treatment agents for natural killer/T-cell lymphoma
Authors
Xiao-Peng Tian
Yi Cao
Jun Cai
Yu-Chen Zhang
Qi-Hua Zou
Jin-Ni Wang
Yu Fang
Jia-Hui Wang
Song-Bin Guo
Qing-Qing Cai
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2023
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-023-01483-9

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