Recent Advances in the Diagnosis and Treatment of Natural Killer Cell Malignancies

Abstract

Natural killer (NK)/T-cell lymphomas are aggressive malignancies. Epstein–Barr virus (EBV) infection in lymphoma cells is invariable. NK/T-cell lymphomas are divided into nasal, non-nasal, and disseminated subtypes. Nasal NK/T-cell lymphomas involve the nasal cavity and the upper aerodigestive tract. Non-nasal NK/T-cell lymphomas involve the skin, gastrointestinal tract, testis and other extranodal sites. Disseminated NK/T-cell lymphoma involves multiple organs, rarely presenting with a leukaemic phase. Lymphoma cells are positive for CD3ε (not surface CD3), CD56, cytotoxic molecules and EBV-encoded small RNA. There is a predilection for Asian and Central/South American populations. Genome-wide association studies have identified lymphoma susceptibility loci in Asian patients. Positron emission tomography computed tomography and plasma EBV DNA quantification are crucial evaluations at diagnosis and follow-up. Stage I/II patients typically receive non-athracycline regimens containing asparaginse, together with sequential/concurrent radiotherapy. Anthracycline-containing regimens are ineffective. Stage III/IV patients are treated with asparaginase-containing regimens, followed by allogeneic haematopoietic stem cell transplantation (HSCT) in suitable cases. Autologous HSCT does not improve outcome. In relapsed/refractory patients, novel approaches are needed, involving PD1/PD-L1 targeting, EBV-specific cytotoxic T-cells, and monoclonal antibodies. Small molecules including histone deacetylase inhibitors may be beneficial in selected patients. Future strategies may include targeting of signalling pathways and driver mutations.

Intravascular NK/T-Cell Lymphoma: What We Know about This Diagnostically Challenging, Aggressive Disease

“…PD-L1 is the ligand of the immune-checkpoint protein PD1 identified on T-lymphocytes. By binding to PD1 on T-lymphocytes and blocking their functions, PD-L1 favors the mechanism of immune evasion by neoplastic cells of ENKTL [ 72 ].…”

“…As previously mentioned, an association between EBV and the PD1/PD-L1 pathway has been noted in different neoplasms, and the overexpression of PD-L1 represents a mechanism of immune evasion in lymphoid cells infected by EBV [ 72 ].…”

“…In ENKTL, PD-L1 overexpression is possibly related to different factors. The EBV-related oncoprotein LMP1 is one of the mechanisms driving PD-L1 overexpression through the NF-kB pathway [ 72 ].…”

“…In ENKTL, both JAK/STAT and NF-kB are usually activated, and multiple recurrent genetic and epigenetic (hypermethylation) alterations have been identified [ 24 , 27 , 73 , 74 , 75 , 76 ]. The JAK/STAT pathway also contributes to PD-L1 overexpression by interacting with the interferon-stimulated response element in the promoter region of PD-L1 [ 72 ].…”

Asparaginase‐related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System ( FAERS ) data and literature review

“…Asparaginase is an important drug in the treatment of acute lymphoblastic leukaemia (ALL) and NK/T-cell lymphomas, including L-asparaginase (L-asp, Erwinia-or E. coli-derived) and pegaspargase (PEG-asp). 1,2 Common adverse reactions of asparaginase include pancreatitis, hepatotoxicity, hypertriglyceridemia, thrombosis, and hypersensitivity, 3 but asparaginase-associated diabetic ketoacidosis (DKA) is rarely reported. A 50-year-old Chinese woman without diabetes in our hospital was diagnosed with B-cell ALL.…”