Due to the specific features and difficulties of extranodal NK/T-cell lymphoma (ENKTCL), specialized treatment strategies are crucial for optimal control of ENKTCL. With our strong experience in the development of therapies for ENKTCL, Protheragen is poised to offer tailored solutions and full-service support to transform ENKTCL therapy research into commercial products.
Extranodal NK/T-cell lymphoma (ENKTCL) is a very uncommon and highly aggressive form of non-Hodgkin lymphoma (NHL) which occurs with Epstein-Barr virus (EBV) infection. In contrast to other types of lymphoma, ENKTCL is characterized by the proliferation of natural killer (NK) cells or cytotoxic T cells. Common sites of presentation of ENKTCL are the nasal cavity, upper aerodigestive tract, skin and the gastrointestinal tract.
Fig.1 The main pathogenesis involved in extranodal NK/T-cell lymphoma (ENKTCL). (Costa, Renata de Oliveira, et al., 2023)
Extranodal NK/T-cell lymphoma (ENKTCL) develops from the oncogenic transformation of NK cells or cytotoxic T-Cells induced by EBV due to a complex interplay of viral, genetic, immune system evasion, and other oncogenic processes. Notable factors of the pathogenesis involve:
Epstein-Barr Virus (EBV) Infection
Oncogenic pathways like NF-kB and JAK/STAT, get activated by the EBV-encoded proteins LMP1 and LMP2A, increasing cellular proliferation while inhibiting apoptosis. Viral miRNAs modify the host gene expression to sustain malignancy.
Genetic Alterations
In ENKTCL, recurrent mutations in STAT3 / STAT5 and DDX3X are notable characteristics. Chromosomal deletions, like 6q21 deletion, which is associated with greatly impaired immune control, further disrupt genomic stability.
Immune Evasion Mechanisms
To manipulate immune checkpoints and inhibit T cell activity, tumors overexpress PD-L1. Dysregulated cytokine conditions like IFN-γ and TNF-α lead to chronic inflammation, facilitating immune evasion and the tumor's advancement.
Tissue Tropism & Microenvironment
ENKTCL exhibits angiocentric growth. Chemokine receptors guide tumor cells to nasal/upper airway tissues, where the microenvironment supports survival via stromal interactions and immune suppression.
Due to its rarity, extranodal NK/T-cell Lymphoma (ENKTCL) has few treatment options available. Current standards of treatment include chemoradiation, especially in advanced or relapsed cases. Issues such as chemotherapy resistance, high relapse rate and EBV-driven immune escape underscore the clear need for immunotherapies and targeted therapies.
| Therapy | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Sintilimab and Decitabine | Blocks PD-1/PD-L1 interaction and reverses epigenetic silencing of tumor suppressor genes. | PD-1/DNA methylation | NCT04279379 | Phase II |
| Pembrolizumab and Radiotherapy | Pembrolizumab: Restores T-cell function. Radiotherapy: Induces DNA damage and tumor cell death. |
PD-1/DNA | NCT04417166 | Phase II |
| Sugemalimab and PGemOx Regimen | Sugemalimab: Inhibits PD-1/PD-L1 axis. PGemOx: Chemotherapy. |
PD-L1/DNA | NCT05700448 | Phase III |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Protheragen utilizes its extensive expertise and innovative technologies to offer distinct diagnostic and therapeutic development services. Our experts are proficient in developing disease models with high precision which allows thorough evaluation of safety, effectiveness, and the mechanism of action for proposed therapeutics.
Protheragen is steadfastly dedicated to meticulously validating and optimizing therapies for extranodal NK/T-cell lymphoma (ENKTCL) through a thorough series of pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
Myeloproliferative Disorders (MPDs)
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