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dc.contributor.author
Vera Lozada, Gabriela  
dc.contributor.author
Minnicelli, Carolina  
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Segges, Priscilla  
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Stefanoff, Gustavo  
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Kristcevic, Flavia  
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Ezpeleta, Joaquin  
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Tapia, Elizabeth  
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Niedobitek, Gerald  
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Barros, Mario Henrique  
dc.contributor.author
Hassan, Rocio  
dc.date.available
2019-11-14T18:08:16Z  
dc.date.issued
2018-05  
dc.identifier.citation
Vera Lozada, Gabriela; Minnicelli, Carolina; Segges, Priscilla; Stefanoff, Gustavo; Kristcevic, Flavia; et al.; Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironment; Taylor & Francis; OncoImmunology; 7; 5; 5-2018; 1-10; e1389821  
dc.identifier.issn
2162-4011  
dc.identifier.uri
http://hdl.handle.net/11336/88902  
dc.description.abstract
Interleukin-10 (IL10) is an immune regulatory cytokine. Single nucleotide polymorphisms (SNPs) in IL10 promoter have been associated with prognosis in adult classical Hodgkin lymphoma (cHL). We analyzed IL10 SNPs −1082 and −592 in respect of therapy response, gene expression and tumor microenvironment (TME) composition in 98 pediatric patients with cHL. As confirmatory results, we found that −1082AA/AG; −592CC genotypes and ATA haplotype were associated with unfavourable prognosis: Progression-free survival (PFS) was shorter in −1082AA+AG (72.2%) than in GG patients (100%) (P = 0.024), and in −592AA (50%) and AC (74.2%) vs. CC patients (87.0%) (P = 0.009). In multivariate analysis, the −592CC genotype and the ATA haplotype retained prognostic impact (HR: 0.41, 95% CI 0.2–0.86; P = 0.018, and HR: 3.06 95% CI 1.03–9.12; P = 0.044, respectively). Our analysis further led to some new observations, namely: (1) Low IL10 mRNA expression was associated with −1082GG genotype (P = 0.014); (2) IL10 promoter polymorphisms influence TME composition;−1082GG/−592CC carriers showed low numbers of infiltrating cells expressing MAF transcription factor (20 vs. 78 and 49 vs. 108 cells/mm2, respectively; P< 0.05); while ATA haplotype (high expression) associated with high numbers of MAF+ cells (P = 0.005). Specifically, −1082GG patients exhibited low percentages of CD68+MAF+ (M2-like) intratumoral macrophages (15.04% vs. 47.26%, P = 0.017). Considering ours as an independent validation cohort, our results give support to the clinical importance of IL10 polymorphisms in the full spectrum of cHL, and advance the concept of genetic control of microenvironment composition as a basis for susceptibility and therapeutic response.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Taylor & Francis  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
CHL  
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MACROPHAGES  
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MAF  
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SINGLE NUCLEOTIDE POLYMORPHISMS (SNP)  
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SURVIVAL  
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TUMOR MICROENVIRONMENT  
dc.subject.classification
Biología Celular, Microbiología  
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Ciencias Biológicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironment  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2019-10-17T14:55:25Z  
dc.journal.volume
7  
dc.journal.number
5  
dc.journal.pagination
1-10; e1389821  
dc.journal.pais
Reino Unido  
dc.description.fil
Fil: Vera Lozada, Gabriela. Instituto Nacional de Cancer; Brasil  
dc.description.fil
Fil: Minnicelli, Carolina. Instituto Nacional de Cancer; Brasil. Universidade Federal do Rio Grande do Norte; Brasil  
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Fil: Segges, Priscilla. Instituto Nacional de Cancer; Brasil  
dc.description.fil
Fil: Stefanoff, Gustavo. Instituto Nacional de Cancer; Brasil  
dc.description.fil
Fil: Kristcevic, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; Argentina  
dc.description.fil
Fil: Ezpeleta, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; Argentina  
dc.description.fil
Fil: Tapia, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; Argentina  
dc.description.fil
Fil: Niedobitek, Gerald. Unfallkrankenhaus Berlin; Alemania  
dc.description.fil
Fil: Barros, Mario Henrique. Unfallkrankenhaus Berlin; Alemania  
dc.description.fil
Fil: Hassan, Rocio. Instituto Nacional de Cancer; Brasil  
dc.journal.title
OncoImmunology  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1080/2162402X.2017.1389821  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/2162402X.2017.1389821