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pmid:33668573
Low Expression of IL-15 and NKT in Tumor Microenvironment Predicts Poor Outcome of MYCN-Non-Amplified Neuroblastoma.
Yu-Mei Liao · Tsai-Hsien Hung · John K Tung · John Yu · Ya-Ling Hsu · Jung-Tung Hung · Alice L Yu
Journal of personalized medicine · 2021 doi:10.3390/jpm11020122
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Experiment
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Complete file
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T cells and natural killer (NK) cells have been shown to play important roles in the neuroblastoma TME. However, few reports address the clinical relevance of natural killer T cells (NKTs) and interleukin-15 (IL-15), one of the crucial cytokines controlling the activation and expansion of NK/NKT cells, in NBL. In this study, we examined NKT immunoscores and IL-15 expression in both MYCN-amplified and MYCN-non-amplified NBL to correlate with clinical outcomes such as event-free survival (EFS) and overall survival (OS). From Gene Expression Omnibus (GEO) datasets GSE45480 (n = 643) and GSE49711 (n = 493), we found that NKT immunoscore and IL-15 expression were both significantly lower in MYCN-amplified NBL, and similar results were observed using our clinical NBL samples (n = 53). Moreover, NBL patients (GEO dataset GSE49711 and our clinical samples) with both lower NKT immunoscore and IL-15 expression exhibited decreased EFS and OS regardless of MYCN gene amplification status. Multivariate analysis further showed that the combination of low NKT immunoscore and low IL-15 expression level was an independent prognostic factor for poor EFS and OS in our NBL patients. These findings provide the rationale for the development of strategy to incorporate IL-15 and NKT cell therapy into the treatment regimen for neuroblastoma.", "claims": [{"id": "claim-method", "statement": "Survival curves were plotted using the Kaplan–Meier method, with the log-rank test applied for comparison. The Cox proportional hazards regression model was employed to identify independent prognostic factors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33668573", "locator": "sections[6] \"2.4. Statistical Analysis\" paragraph 2", "quote": "Survival curves were plotted using the Kaplan–Meier method, with the log-rank test applied for comparison. 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The archival sample data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GEO data presented in this study are openly available in GSE49711 and GSE45480. The archival sample data presented in this study are available on request from the corresponding author. 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"Clinical and pathological characteristics of 53 neuroblastoma (NBL) patients.", "structure": {"pmcid": "PMC7918138", "section_index": 4, "section_title": "2.2. 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Lower Expression of Vα24 or IL-15 Is Associated with Decreased Overall Survival in NBL Patients", "row_count": 16, "column_count": 4}, "table": {"label": "Table 3", "caption": "Cox regression analyses of the various factors associated with overall survival in NBL patients (n = 53).", "rows": [["Event-Free Survival", "", ""], ["Variables", "HR (95% CI)", "Favorable/Unfavorable", "p"], ["Univariate analysis", "", ""], ["Stage", "3.69 (1.43–9.49)", "1, 2, 3, 4S/4", "0.007"], ["Risk group", "6.63 (2.18–20.15)", "Low, Middle/High", "0.001"], ["Age at diagnosis_1.5", "3.85 (1.46–10.17)", "<1.5 years/≥1.5 years", "0.006"], ["Vα24", "13.24 (1.76–99.68)", "Low/High", "0.012"], ["IL-15", "5.00 (1.46–17.21)", "Low/High", "0.011"], ["Vα24 and IL-15", "5.50 (1.81–16.6)", "All Low/Others", "0.003"], ["Multivariate analysis", "", ""], ["Stage", "8.51 (0.83–87.84)", "1, 2, 3, 4S/4", "0.07"], ["Risk group", "21.14 (1.79–249.09)", "Low, Middle/High", "0.015"], ["Age at diagnosis_1.5", "2.43 (0.73–8.08)", "<1.5 years/≥1.5 years", "0.147"], ["Vα24", "10.26 (1.33–79.36)", "Low/High", "0.026"], ["IL-15", "4.95 (1.43–17.12)", "Low/High", "0.012"], ["Vα24 and IL-15", "15.55 (1.99–121.41)", "All Low/Others", "0.009"]], "row_count": 16, "column_count": 4, "numeric_cells": 37, "header_rows": 2, "locator": "section[11]/table-wrap[2]#jpm-11-00122-t003"}}], "gaps": ["asset:data:geo:GSE45480 not downloaded", "asset:data:geo:GSE45480 licence not read", "asset:data:geo:GSE49711 not downloaded", "asset:data:geo:GSE49711 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Survival curves were plotted using the Kaplan–Meier method, with the log-rank test applied for comparison. 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