|Table of Contents|

Research progress in PD-1/PD-L1 inhibitors for the treatment of extranodal NK/T-cell lymphoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 08
Page:
1559-1562
Research Field:
Publishing date:

Info

Title:
Research progress in PD-1/PD-L1 inhibitors for the treatment of extranodal NK/T-cell lymphoma
Author(s):
HUANG Shi; ZHAO Yunlin; KE Shuhui; LIN Dandan
Oncology Department,Renmin Hospital of Wuhan University,Hubei Wuhan 430060,China.
Keywords:
extranodal NK/T-cell lymphoma; immune checkpoint inhibitor; chemotherapy; biomarker
PACS:
R733.4
DOI:
10.3969/j.issn.1672-4992.2024.08.034
Abstract:
Extranodal NK/T-cell lymphoma (ENKTCL) is a rare and highly aggressive non-Hodgkin lymphoma closely associated with Epstein-Barr virus infection.At present,there are many therapeutic methods for ENKTCL,such as chemotherapy,radiotherapy,hematopoietic stem cell transplantation and immunotherapy.In recent years,with the in-depth study of the pathogenesis of ENKTCL,immune checkpoint therapy targeting PD-1/PD-L1 has been considered to hold significant clinical value.This article provides an overview of the mechanisms of PD-1/PD-L1 inhibitors,summarizes their clinical research progress in the field of ENKTCL treatment,and discusses the selection of predictive biomarkers for treatment efficacy.Additionally,it outlines the limitations faced by PD-1/PD-L1 inhibitors in the treatment of ENKTCL as well as the prospects for future development.

References:

［1］ XIONG J,CUI BW,WANG N,et al.Genomic and transcriptomic characterization of natural killer T cell lymphoma［J］.Cancer Cell,2020,37(3):403-419.
［2］ TSE E,KWONG YL.How I treat NK/T-cell lymphomas［J］.Blood,2013,121(25):4997-5005.
［3］ FOX CP,CIVALLERO M,KO YH,et al.Survival outcomes of patients with extranodal natural-killer T-cell lymphoma:a prospective cohort study from the international T-cell project［J］.Lancet Haematol,2020,7(4):e284-e294.
［4］ YAN Z,YAO S,WANG Z,et al.Treatment of extranodal NK/T-cell lymphoma:From past to future［J］.Front Immunol,2023,14:1088685.
［5］ LIM SH,HONG JY,LIM ST,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［J］.Ann Oncol，2017，28(9):2199-2205.
［6］ FREEMAN GJ,LONG AJ,IWAI Y,et al.Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation［J］.J Exp Med,2000,192(7):1027-1034.
［7］ ZHAO Y,HARRISON DL,SONG Y,et al.Antigen-presenting cell-intrinsic PD-1 neutralizes PD-L1 in cis to attenuate PD-1 signaling in T cells［J］.Cell Rep,2018,24(2):379-390.
［8］ NAGATO T,OHKURI T,OHARA K,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［J］.Cancer Immunol Immunother,2017,66(7):877-890.
［9］ BI XW,WANG H,ZHANG WW,et al.PD-L1 is upregulated by EBV-driven LMP1 through NF-kappaB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma［J］.J Hematol Oncol,2016,9(1):109.
［10］ SONG TL,NAIRISMAGI ML,LAURENSIA Y,et al.Oncogenic activation of the STAT3 pathway drives PD-L1 expression in natural killer/T-cell lymphoma［J］.Blood,2018,132(11):1146-1158.
［11］ KWONG YL,CHAN T,TAN D,et al.PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase［J］.Blood,2017,129(17):2437-2442.
［12］ LI X,CHENG Y,ZHANG M,et al.Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma［J］.J Hematol Oncol,2018,11(1):15.
［13］ HOY SM.Sintilimab:First global approval［J］.Drugs,2019,79(3):341-346.
［14］ TAO R,FAN L,SONG Y,et al.Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma:a multicenter,single-arm,phase 2 trial (ORIENT-4)［J］.Signal Transduct Target Ther,2021,6(1):365.
［15］ KIM SJ,LIM JQ,LAURENSIA Y,et al.Avelumab for the treatment of relapsed or refractory extranodal NK/T-cell lymphoma:an open-label phase 2 study［J］.Blood,2020,136(24):2754-2763.
［16］ QI SN,LI YX,SPECHT L,et al.Modern radiation therapy for extranodal nasal-type NK/T-cell lymphoma:Risk-adapted therapy,target volume,and dose guidelines from the international lymphoma radiation oncology group［J］.Int J Radiat Oncol Biol Phys,2021,110(4):1064-1081.
［17］ CAI J,LIU P,HUANG H,et al.Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma［J］.Signal Transduct Target Ther,2021,6(1):184-192.
［18］ HUANG H.Clinical outcome of P-Gemox (pegaspargase,gemcitabine,oxaliplatin) for the patients with newly diagnosed stage III/IV or relapsed/refractory extranodal natural killer/T cell lymphoma［J/OL］.Blood,2015,126(23):1521［2023-10-02］.https://www.sciencedirect.com.DOI:10.1182/blood.v126.23.1521.1521.
［19］ YAN G.P-Gemox regimen(pegaspargase,gemcitabine,oxaliplatin) for extranodal natural killer cell lymphoma:10 years' real-world clinical experience from China［J/OL］.Blood,2018,132(S1):1659［2023-10-02］.https://ashpublications.org.DOI:10.1182/blood-2018-99-116551.
［20］ SUN P,LI Y,LI C,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［J］.Am J Hematol,2023,98(7):1043-1051.
［21］ 马军,沈志祥,朱军,等.西达本胺治疗外周T细胞淋巴瘤中国专家共识(2018年版)［J］.中国肿瘤临床,2018,45(15):763-768. MA J,SHEN ZX,ZHU J,et al.Chinese expert consensus on chidamide for peripheral T-cell lymphoma (2018 edition)［J］.Chinese Journal of Clinical Oncology,2018,45(15):763-768.
［22］ CHEN J,ZUO Z,GAO Y,et al.Aberrant JAK-STAT signaling-mediated chromatin remodeling impairs the sensitivity of NK/T-cell lymphoma to chidamide［J］.Clin Epigenetics,2023,15(1):19.
［23］ GARCHA HK,NAWAR N,SORGER H,et al.High efficacy and drug synergy of HDAC6-selective inhibitor NN-429 in natural killer (NK)/T-cell lymphoma［J］.Pharmaceuticals (Basel),2022,15(11):1321.
［24］ HUANG H,GAO Y,WANG X,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)［J］.Hematological Oncology,2021,39(S2):298-300.
［25］ WEN T,SUN G,JIANG W,et al.Histone deacetylases inhibitor chidamide synergizes with humanized PD1 antibody to enhance T-cell chemokine expression and augment IFN-gamma response in NK-T cell lymphoma［J］.EBioMedicine,2023,87:104420.
［26］ XU JY,XU XH,CHEN JY,et al.Sustained remission of multi-line relapsed extranodal NK/T-cell lymphoma,nasal type,following sintilimab and chidamide:A case report［J］.Medicine (Baltimore),2021,100(10):e24824.
［27］ JO JC,KIM M,CHOI Y,et al.Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma,nasal type［J］.Ann Hematol,2017,96(1):25-31.
［28］ CHO J,KIM SJ,PARK WY,et al.Immune subtyping of extranodal NK/T-cell lymphoma:a new biomarker and an immune shift during disease progression［J］.Mod Pathol,2020,33(4):603-615.
［29］ KIM WY,JUNG HY,NAM SJ,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［J］.Virchows Arch,2016,469(5):581-590.
［30］ FENG Y,JING C,YU X,et al.Predicting treatment response of patients with extranodal natural killer/T-cell lymphoma based on levels of PD-L1 mRNA and soluble PD-L1［J］.Hematol Oncol,2020,38(4):467-477.
［31］ KIM SJ,RYU KJ,PARK B,et al.Exosomal and soluble programed death-ligand 1 (PD-L1) predicts responses to pembrolizumab in patients with extranodal NK/T-cell lymphoma［J］.Cancers (Basel),2022,14(22):5618.
［32］ LIM JQ,HUANG D,TANG T,et al.Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma［J］.Leukemia,2020,34(12):3413-3419.

Memo

Memo:
National Natural Science Foundation of China(No.32270951）；国家自然科学基金面上项目(编号：32270951)
Last Update: 1900-01-01