ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2020
Immune subtyping of extranodal NK/T-cell lymphoma: a new biomarker and an immune shift during disease progression.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 54 citations in OpenAlex.
- Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study.Annals of hematology · 2021Trial
- Article
- Selinexor plus tislelizumab in patients with relapsed/refractory natural killer/T-cell lymphoma after failure of PD-1 blockade: the phase 1b TOUCH trial.The oncologist · 2026Article
- The increased co-expression of SLC7A11 and PD-L1 was associated with poor prognosis in extranodal natural killer T-cell lymphoma patients.Cancer immunology, immunotherapy : CII · 2026Article
- Long-term outcomes of 40 Gy CCRT with weekly cisplatin and systemic chemotherapy in limited-stage ENKTL.Blood advances · 2026Article
- Clinicopathologic implications of sphingosine-1-phosphate pathway in extranodal NK/T-cell lymphoma according to immune subtype.Scientific reports · 2026Article
- Epstein-barr virus-encoded small RNA incorporated prognostic model enables precision risk stratification and guides treatment decisions in peripheral t-cell lymphoma: a multicenter retrospective cohort.Annals of hematology · 2025Article
- The Significance of the Microenvironment in T/Nk-Cell Neoplasms.International journal of molecular sciences · 2025Review
- Extranodal NK/T-cell lymphoma: an update of the molecular characterization of the tumor and microenvironment, and its clinical implications.The Lancet regional health. Western Pacific · 2025Review
- Early growth response 1 as a key regulator of PD-L1 expression and immune evasion in extranodal NK/T-cell lymphoma.Blood cancer journal · 2025Article
- Clinical Impact of Microbiome Characteristics in Treatment-Naïve Extranodal NK/T-Cell Lymphoma Patients.Cancer research and treatment · 2025Article
- Review
- MiR-340-5p regulates PD-L1 and predicts pembrolizumab response in extranodal NK/T-cell lymphoma.Scientific reports · 2025Article
- Modeling NK-cell lymphoma in mice reveals its cell-of-origin and microenvironmental changes and identifies therapeutic targets.Nature communications · 2024Article
- Resistance mechanisms and potential therapeutic strategies in relapsed or refractory natural killer/T cell lymphoma.Chinese medical journal · 2024Review
- Optimization of immune checkpoint inhibitor treatment planning for relapsed or refractory extranodal NK/T cell lymphoma.Annals of hematology · 2024Article
- Analysis of mutation profiles in extranodal NK/T-cell lymphoma: clinical and prognostic correlations.Annals of hematology · 2024Article
- Immunotyping of peripheral blood lymphocytes by flow cytometry reveals Th cell as a potential prognostic biomarker for extranodal NK/T-cell lymphoma.Annals of hematology · 2024Article
- Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea.Cancer research and treatment · 2024Article
- Biology and genetics of extranodal mature T-cell and NKcell lymphomas and lymphoproliferative disorders.Haematologica · 2023Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
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Abstract
Extranodal NK/T-cell lymphoma is an aggressive lymphoma that is strongly associated with Epstein-Barr virus infection. Although some extranodal NK/T-cell lymphoma patients have shown responses to immune checkpoint blockade, biomarkers for predicting extranodal NK/T-cell lymphoma patient response to immunotherapy have not yet been defined. To understand the tumor immune microenvironment, we analyzed the expression of 579 immune-related genes and characterized the immune cells using immunohistochemistries and in situ hybridization for EBER. Based on comprehensive analyses, we developed an immune subtyping model that classifies extranodal NK/T-cell lymphoma patients into four tumor immune microenvironment subgroups using three immunohistochemical markers (FoxP3, PD-L1, and CD68). The four tumor immune microenvironment subgroups were named immune tolerance, immune evasion-A, immune evasion-B, and immune silenced. The immune tolerance group was characterized by high-Treg counts and was frequently observed in early stage, and nasal extranodal NK/T-cell lymphoma. The immune evasion group showed high cytotoxic T-cell counts and high PD-L1 expression but low Treg counts. In the immune-silenced group, almost all immune responses were exhausted, most patients were at an advanced stage, and had the poorest disease prognosis among the tumor immune microenvironment subgroups. In some patients (n = 3), a shift in the tumor immune microenvironment subgroup classification was observed in sequential biopsies. The response rate to pembrolizumab, an anti-PD-1 antibody, was 100% (1/1) in the immune tolerance group, 60% (3/5) in the immune evasion group, and 0% (0/5) in the immune-silenced group. We classified extranodal NK/T-cell lymphoma into four tumor immune microenvironment subgroups using a new classification system. In conclusion, we propose that the tumor immune microenvironment of extranodal NK/T-cell lymphoma may change during disease progression and may serve as a useful biomarker for immunotherapy.
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