Blood Res 2021; 56(4):
Published online December 31, 2021
https://doi.org/10.5045/br.2021.2021123
© The Korean Society of Hematology
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Extranodal NK/T cell lymphomas (ENKTCLs) are aggressive cancers that originate from Epstein-Barr virus (EBV) infections. Defects in genes related to antigen presentation and T-cell activation, including human leukocyte antigen (
ENKTCLs are EBV-associated lymphomas with aggressive clinical behaviors. ENKTCL patients typically present with destructive necrotizing tumor masses that affect the upper aerodigestive tract, including the nose, nasopharynx, and paranasal sinuses. Some patients manifest more advanced stages in the lymph nodes, skin, liver, and bone marrow, indicating very poor outcomes. Current treatments include local radiotherapy and combination chemotherapy with L-asparaginase. Immunotherapy and targeted therapy are emerging treatments that may improve patient outcomes, especially in patients with advanced disease [1].
The incidence of ENKTCLs is higher in East Asia and Latin America than in other parts of the world. The genetic background of the HLA system and immune regulation is a possible explanation for the different frequencies among ethnic groups. Two genome-wide association studies conducted in East Asian populations revealed that
EBV infection associated with ENKTCL is classified as a type II latency program because tumor cells usually express EBV-encoded small RNA (EBER), EBV nuclear antigen 1 (EBNA1), and latent membrane protein 1 (LMP1). LMP1 is a viral oncoprotein that can promote abnormal NK/T cell proliferation and may enhance genomic instability via overexpression of activation-induced cytidine deaminase (AID) [4], leading to further oncogenic mutations.
In addition to the HLA system,
Using next-generation sequencing technology, genetic alterations in ENKTCLs were shown to involve various pathways, including epigenetic regulators (58%), RNA helicases (21%), Janus kinase-signal transducer and activator of transcription (JAK-STAT) (26%), other signal transductions (11%), tyrosine phosphatases (26%), tumor suppressors (11%), and immune surveillance (32%) [10-12]. In our study, whole-exome sequencing also revealed abnormalities in ENKTCLs involving HLAs and related genes, which were somatic mutations and copy number variation, accounting for 32% [10]. Loss-of-function mutations in
In summary, defective viral antigen presentation may promote lymphomagenesis and progression. Additionally, the PD/PD-L pathway is employed by tumor cells to evade the immune system and can serve as a molecular target for therapy. Studies involving larger numbers of patients with ENKTCL are required to correlate the HLA and PD/PD-L defects with clinical outcomes and clinical responses to anti-PD1 treatments.
No potential conflicts of interest relevant to this article were reported.
Blood Res 2021; 56(4): 209-211
Published online December 31, 2021 https://doi.org/10.5045/br.2021.2021123
Copyright © The Korean Society of Hematology.
Chantana Polprasert, M.D., Kitsada Wudhikarn, M.D., Ponlapat Rojnuckarin, M.D., Ph.D.
Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Extranodal NK/T cell lymphomas (ENKTCLs) are aggressive cancers that originate from Epstein-Barr virus (EBV) infections. Defects in genes related to antigen presentation and T-cell activation, including human leukocyte antigen (
ENKTCLs are EBV-associated lymphomas with aggressive clinical behaviors. ENKTCL patients typically present with destructive necrotizing tumor masses that affect the upper aerodigestive tract, including the nose, nasopharynx, and paranasal sinuses. Some patients manifest more advanced stages in the lymph nodes, skin, liver, and bone marrow, indicating very poor outcomes. Current treatments include local radiotherapy and combination chemotherapy with L-asparaginase. Immunotherapy and targeted therapy are emerging treatments that may improve patient outcomes, especially in patients with advanced disease [1].
The incidence of ENKTCLs is higher in East Asia and Latin America than in other parts of the world. The genetic background of the HLA system and immune regulation is a possible explanation for the different frequencies among ethnic groups. Two genome-wide association studies conducted in East Asian populations revealed that
EBV infection associated with ENKTCL is classified as a type II latency program because tumor cells usually express EBV-encoded small RNA (EBER), EBV nuclear antigen 1 (EBNA1), and latent membrane protein 1 (LMP1). LMP1 is a viral oncoprotein that can promote abnormal NK/T cell proliferation and may enhance genomic instability via overexpression of activation-induced cytidine deaminase (AID) [4], leading to further oncogenic mutations.
In addition to the HLA system,
Using next-generation sequencing technology, genetic alterations in ENKTCLs were shown to involve various pathways, including epigenetic regulators (58%), RNA helicases (21%), Janus kinase-signal transducer and activator of transcription (JAK-STAT) (26%), other signal transductions (11%), tyrosine phosphatases (26%), tumor suppressors (11%), and immune surveillance (32%) [10-12]. In our study, whole-exome sequencing also revealed abnormalities in ENKTCLs involving HLAs and related genes, which were somatic mutations and copy number variation, accounting for 32% [10]. Loss-of-function mutations in
In summary, defective viral antigen presentation may promote lymphomagenesis and progression. Additionally, the PD/PD-L pathway is employed by tumor cells to evade the immune system and can serve as a molecular target for therapy. Studies involving larger numbers of patients with ENKTCL are required to correlate the HLA and PD/PD-L defects with clinical outcomes and clinical responses to anti-PD1 treatments.
No potential conflicts of interest relevant to this article were reported.