Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type

Jo, Jae Cheol; Kim, Misung; Choi, Yun Suk; Kim, Hyun Jung; Kim, Ji Eun; Chae, Seoung Wan; Kim, Hawk; Jeong, Hee

doi:10.1007/s00277-016-2818-4

Cited by 97 publications

(80 citation statements)

References 22 publications

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“…18 Another recent study also found that ENKTL patients with PD-L1 positivity in tumor cells had a trend toward improved OS compared with the negative control. 21 Contrary to these results, Bi et al and Muhamad et al found that PD-L1 expression in lymphoma cell tissue exhibited remarkably worse OS in ENKTL patients, 19 which was similar to the results of our study. Therefore, a single biomarker of PD-L1 for predicting the prognosis of ENKTL patients might have some limitations.…”

Section: Discussionsupporting

confidence: 88%

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<p>A New Immunological Prognostic Model Based on Immunohistochemistry for Extranodal Natural Killer/T-Cell Lymphoma Patients After Non-Anthracycline-Based Chemotherapy</p>

Lam

Huang

Fang

et al. 2020

CMAR

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These authors contributed equally to this work Purpose: Programmed death ligand 1 (PD-L1) has been proposed as an important prognostic factor in many types of cancer. However, the role of predicting the prognosis of PD-L1 in extranodal natural killer/T-cell lymphoma (ENKTL) was controversial. Combining other biomarkers might enhance its predictive power. This study aims to evaluate the prognostic value of PD-L1 in conjunction with tumor-infiltrating FoxP3+Tregs for ENKTL after nonanthracycline-based chemotherapy. Patients and Methods: A total of 81 patients with ENKTL were included in this study. Clinicopathological characteristics were collected, and prognostic significance of PD-L1 in neoplastic cells (nPD-L1) and tumor-infiltrating FoxP3+Tregs were evaluated. Results: Patients with nPD-L1-positive had significantly inferior overall survival (OS) and progression-free survival (PFS) compared with nPD-L1-negative (3-year OS, 37.2% vs 67.3%, p = 0.014; 3-year PFS, 31.0% vs 61.8%, p =0.010, respectively). Patients who had low FoxP3+Tregs had significantly inferior OS and PFS compared with high FoxP3+Tregs (3-year OS, 36.4% vs 63.0%, p = 0.004; 3-year PFS, 31.7% vs 56.3%, p = 0.020, respectively). The results of multivariate analysis showed that nPD-L1 positivity (HR 6.629, 95% CI 1. 966-22.350, p=0.002) and low FoxP3+Tregs (HR 7.317, p=0.001) were independent predictors of inferior OS. Using these 2 variables, we constructed a new prognostic model that singled out 3 groups with different risk profiles: group 1, no adverse factors; group 2, 1 adverse factor; and group 3, 2 adverse factors. The 3-year OS rates of group 1, group 2, and group 3 were 93.3%, 46.6% and 20.8%, respectively (p<0.001), and the 3-year PFS rates were 86.7%, 40.8% and 15.0%, respectively (p=0.001).Conclusion: This study is the first to validate the prognostic value of nPD-L1 and tumorinfiltrating FoxP3+Tregs in ENKTL; the new immunological prognostic model might be used to stratify ENKTL patients in clinical trials for new therapeutic strategies.

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Section: Discussionsupporting

confidence: 88%

“…[12][13][14][15][16][17] However, the results regarding the prognostic significance of PD-L1 in ENKTL are conflicting. [18][19][20][21][22] Based on these observations, the role of predicting the prognosis of PD-L1 has not been fully elucidated, and its use in combination with other biomarkers might enhance its predictive power.…”

Section: Introductionmentioning

confidence: 99%

<p>A New Immunological Prognostic Model Based on Immunohistochemistry for Extranodal Natural Killer/T-Cell Lymphoma Patients After Non-Anthracycline-Based Chemotherapy</p>

Lam

Huang

Fang

et al. 2020

CMAR

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“…At present, the relationship between the expression of PD-L1 and the prognosis of patients with NHL remains controversial. Some studies have proposed that positive PD-L1 expression correlates with a poor prognosis 15-19 , while other studies have shown that positive PD-L1 expression does not correlate with prognosis or correlates with a good prognosis 20-23 . …”

Section: Discussionmentioning

confidence: 99%

The prognostic value of programmed cell death ligand 1 expression in non-Hodgkin lymphoma: a meta-analysis

Zhao¹,

Zhang²,

Meng

et al. 2018

Cancer Biology & Medicine

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Objective:Although the prognostic value of programmed cell death-ligand 1 (PD-L1) expression in non-Hodgkin lymphoma (NHL) has been evaluated in many studies, the results remain controversial. To investigate the prognostic role of PD-L1 expression and the association between PD-L1 expression and clinicopathological features of NHL, we performed a meta-analysis.Methods:The PubMed, EMBASE, and Cochrane Library databases were searched up to November 30, 2017. The hazard ratio (HR), 95% confidence interval (CI), and odds ratios (OR) with 95% CIs were combined to evaluate the association of PD-L1 expression with overall survival (OS) and clinicopathological features. Review manager 5.3 and STATA 12.0 were used in this meta-analysis.Results:A total of 2,005 patients across nine studies were enrolled in our meta-analysis, and the pooled results showed that high PD-L1 expression was associated with a poor prognosis (HR=2.04, 95% CI: 1.18–3.54, P=0.01). In the subgroup analysis according to histology types, pooled results demonstrated that an increased PD-L1 expression was an unfavorable prognostic factor for diffuse large B-cell lymphoma (HR=1.92, 95% CI: 1.06–3.48, P=0.03) but not for natural killer/T-cell lymphoma (HR=2.41, 95% CI: 0.47–12.22, P=0.29). Pooled ORs indicated that PD-L1 expression was higher in NHL with international prognostic indices of ≥3. However, PD-L1 expression had no correlation with gender, age, disease stage, lactate dehydrogenase level, B symptoms, and germinal center B-cell-like lymphoma. Conclusions:High PD-L1 expression was a poor prognostic biomarker in patients with NHL. Because of our limited sample size, high-quality studies with larger sample sizes are needed to validate our results.

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“…NK/T-cell lymphoma cells express programmed death protein ligand 1 (PDL1), ligand of the inhibitory receptor PD1 on effector T-cells [82, 83]. PDL1 expression has been shown to be associated with EBV infection in lymphoma cells.…”

Section: Introductionmentioning

confidence: 99%

The diagnosis and management of NK/T-cell lymphomas

2017

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Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignancy of putative NK-cell origin, with a minority deriving from the T-cell lineage. Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most commonly (80%) in the nose and upper aerodigestive tract, less commonly (20%) in non-nasal areas (skin, gastrointestinal tract, testis, salivary gland), and rarely as disseminated disease with a leukemic phase. Genetic analysis showed mutations of genes involved in the JAK/STAT pathway, RNA assembly, epigenetic regulation, and tumor suppression. In initial clinical evaluation, positron emission tomography computed tomography, and quantification of plasma EBV DNA are mandatory as they are useful for response monitoring and prognostication. In stage I/II diseases, combined chemotherapy and radiotherapy (sequentially or concurrently) is the best approach. Conventional anthracycline-containing regimens are ineffective and should be replaced by non-anthracycline-containing regimens, preferably including L-asparaginase. Radiotherapy alone is associated with high systemic relapse rates and should be avoided. In stage III/IV diseases, non-anthracycline-regimens-containing L-asparaginase are the standard. In relapsed/refractory cases, blockade of the programmed death protein 1 has recently shown promising results with high response rates. In the era of effective non-anthracycline-containing regimens, autologous haematopoietic stem cell transplantation (HSCT) has not been shown to be beneficial. However, allogeneic HSCT may be considered for high-risk or advanced-stage patients in remission or relapsed/refractory patients responding to salvage therapy. Prognostic models taking into account presentation, interim, and end-of-treatment parameters are useful in triaging patients to different treatment strategies.

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Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type

Cited by 97 publications

References 22 publications

<p>A New Immunological Prognostic Model Based on Immunohistochemistry for Extranodal Natural Killer/T-Cell Lymphoma Patients After Non-Anthracycline-Based Chemotherapy</p>

<p>A New Immunological Prognostic Model Based on Immunohistochemistry for Extranodal Natural Killer/T-Cell Lymphoma Patients After Non-Anthracycline-Based Chemotherapy</p>

The prognostic value of programmed cell death ligand 1 expression in non-Hodgkin lymphoma: a meta-analysis

The diagnosis and management of NK/T-cell lymphomas

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