Immune subtyping of extranodal NK/T-cell lymphoma: a new biomarker and an immune shift during disease progression

Cho, Junhun; Kim, Seok Jin; Park, Woong-Yang; Kim, Jin-Ho; Woo, Jeongmin; Kim, Ga Hyun; Yoon, Sang Eun; Ko, Young Hyeh; Kim, Won Seog

doi:10.1038/s41379-019-0392-8

Cited by 42 publications

(39 citation statements)

References 40 publications

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“…However, limited cutaneous forms have a longer median survival than extracutaneous variants. To investigate this controversial clinical course, several studies have focused on the potential role of the tumor microenvironment in malignant behavior and progression of tumorigenesis [12,13]. Immune cells including mast cells, macrophages, and T or B lymphocytes are considered as speci c pathogenetic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Primary Cutaneous Extranodal NK/T-Cell Lymphoma, Nasal Type, with Extensive Skin Lesions: A Case Report with Immune Cell Shift

Xie¹,

Shi²,

Kong³

2020

Preprint

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Background: Primary cutaneous extranodal natural killer (NK)/T-cell lymphoma, nasal type (PC-ENKTL), is a rare entity of malignancies of NK cells or cytotoxic T cells, characterized by an association with Epstein-Barr virus (EBV) infection. Despite its aggressive behavior, PC-ENKTL is mostly found as a localized disease. Data regarding PC-ENKTL with generalized skin lesions have only rarely been characterized in clinical studies so far. Case presentation: We present a case of PC-ENKTL, nasal type, in a 38-year–old female with a history of disseminated cutaneous plaques, ulcers and painful nodules that originated in her right leg skin as a small raised papule and expanded quickly over the entire body, ranging in diameter from 1 cm to 6 cm. The patient did not show any involvement of other sites except skin. Histologic, immunophenotypic, genetic and clinical features consistent with the diagnosis of primary cutaneous NK/T-cell lymphoma, nasal type. The status of immune cells was analyzed using a panel of monoclonal antibodies and revealed negative stain for CD163, CD68, programmed cell death (PD-1)/programmed cell death l ligand 1(PD-L1), and FoxP3. Chemotherapy followed by radiotherapy was planned but the patient was experienced disease progression and died at 3 months as a result of lymphoma.Conclusions: In contrast to NK/T-cell lymphoma with localized disease, PC-ENKTL with generalized skin lesions tend to be more aggressive, with short survival and extremely poor response to therapy. We propose that the immune cell shift may be related to the severity of the patient.

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Section: Discussionmentioning

confidence: 99%

Primary Cutaneous Extranodal NK/T-Cell Lymphoma, Nasal Type, with Extensive Skin Lesions: A Case Report with Immune Cell Shift

Xie¹,

Shi²,

Kong³

2020

Preprint

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“…Recently, Cho et al [72] proposed a new immune subtyping model that is effective in predicting the response with checkpoint inhibitors. In the model, ENKTLs were classified into four tumor immune microenvironment subgroups (immune tolerance, immune evasion-A, immune evasion-B, and immune silenced) using three immunohistochemical markers (FoxP3, PD-L1, and CD68).…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Extranodal NK/T cell lymphoma

Jeong

2020

Blood Res

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Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a distinct subtype of Non-Hodgkin's lymphoma mainly involving the nasal area. Since the entity was first recognized, treatment strategies have been evolving from anthracycline-based chemotherapy and radiotherapy to L-asparaginase containing regimens and recently immune checkpoint inhibitors. With the currently used combined chemotherapy and radiotherapy, more than 70% of patients with localized disease can be cured. L-asparaginase containing regimens have significantly improved treatment outcomes among patients with advanced disease. However, the treatment outcomes of patients with disease refractory to L-asparaginase containing regimens or who experience recurrence remain poor. In this article, we cover the current treatments for ENKTL and emerging treatment approaches.

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“…In their previous work on immune subtyping of ENKTL, 4 the authors demonstrated a correlation between outcomes with pembrolizumab in the treatment of relapsed or refractory ENKTL and the extent of PD-L1 expression as described by a PD-L1 score. The score represents a percentage of total PD-L1-positive cells, including tumor-associated macrophages among tumor cells, and a score of .10 was considered high.…”

mentioning

confidence: 95%

“…The conventional approach to understanding the biology of the human memory B-cell compartment has focused on studying peripheral blood and secondary lymphoid tissues, largely focusing on tonsil and spleen. [2][3][4] Previous studies using gut-associated lymphoid tissues (GALTs) led to increased understanding of MBC subsets and deeper understanding of B-cell biology in lymphoid tissues, but gut tissue itself was not evaluated. 5 Not until now has a comprehensive analysis of B-cell lineages across multiple lymphoid and nonlymphoid tissues been performed.…”

mentioning

confidence: 99%