ĮNKTCL is usually classified according to the origin of the lesion into upper aerodigestive tract (UAT) and the non-upper aerodigestive tract (non-UAT) type, and the prognosis and treatment response of the latter are significantly worse than those of the former.
Therefore, to classify and diagnose ENKTCL, it is necessary to detect expression of CD2, CD56, cytoplasmic CD3 epsilon and cytotoxic molecules such as granzyme B and TIA1 as well as EBV-encoded RNA (EBER) positivity. Known mutations associated with ENKTCL, such as gene amplification, deletion and mutation including in cell cycle regulators Rb, TP53, PRDM1, CDKN and FOXO3, are shared with other subtypes of lymphoma, with no specificity. It has been speculated that EBV infection in childhood and pesticides may be risk factors. ENKTCL is predominant in young and middle-aged people, with a higher incidence in males than in females. The cause of the regional difference in prevalence is related to environmental and genetic factors, as recent studies based on the SEER registry show that the rate of ENKTCL is much higher in Asian/Pacific Islanders and Hispanics than in other populations. According to Chinese statistics, ENKTCL constitutes 6.4% of non-Hodgkin lymphoma, and more than 20% of mature T- and NK-cell lymphoma. Its incidence in Asia and South America is approximately 10%, though it is as low as 1% in North America and Western Europe. This article reviews recent advances in ENKTCL immunotherapy as a promising treatment for this fatal disease.Įxtranodal natural killer/T cell lymphoma (ENKTCL) is an aggressive haematological malignancy that is frequently found in the upper aerodigestive tract but can involve non-nasal sites, such as the gastrointestinal tract, skin, soft tissue and testis. Via another signalling pathway the JAK/STAT pathway, upregulation and activation and mutation of genes promotes proliferation and ENKTCL lymphomagenesis, and JAK inhibitors have thus been applied. On the basis of this mechanism, a variety of small molecular inhibitors, such as anti-PD-1 antibodies, NF-κB inhibitors, EBV antigens, and LMP1 and LMP2 antigens, can be applied. Binding of PD-L1 to PD-1 expressing cytotoxic T cells causes apoptosis and inactivation of T lymphocytes, achieving immune escape. EBV-driven overexpression of latent membrane proteins activates the pro-proliferation NF-κB/MAPK signalling pathway and leads to high PD-L1 expression. In addition to these therapies that target cell surface antigens, therapies targeting intracellular signalling pathways and the microenvironment are considerably beneficial. Indeed, it has been proven that targeted therapies such as anti-CD30 antibodies and naked anti-CD38 antibodies are effective. Immunotherapy is a promising treatment for ENKTCL. However, the overall survival (OS) rate of advanced stage patients is not satisfactory compared with patients with non-advanced-stage disease. Novel therapeutic strategies including L-asparaginase-containing regimens, radiotherapy, sequential chemotherapy and radiotherapy, and concurrent chemoradiotherapy (CCRT) have remarkably improved outcomes. Although the clinical outcome of anthracycline-based chemotherapy was dismal because of multidrug resistance (MDR). Extranodal NK/T cell lymphoma, nasal type, is a rare type of non-Hodgkin’s lymphoma (NHL), and the aetiology is not fully understood.
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