Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironment
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 microenvironme...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-05-01
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| Series: | OncoImmunology |
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| Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1389821 |
| _version_ | 1818976294302384128 |
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| author | Gabriela Vera-Lozada Carolina Minnicelli Priscilla Segges Gustavo Stefanoff Flavia Kristcevic Joaquin Ezpeleta Elizabeth Tapia Gerald Niedobitek Mário Henrique M. Barros Rocio Hassan |
| author_facet | Gabriela Vera-Lozada Carolina Minnicelli Priscilla Segges Gustavo Stefanoff Flavia Kristcevic Joaquin Ezpeleta Elizabeth Tapia Gerald Niedobitek Mário Henrique M. Barros Rocio Hassan |
| author_sort | Gabriela Vera-Lozada |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T16:09:34Z |
| format | Article |
| id | doaj.art-843e6e7b40c946a988e416fd87f7be58 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-20T16:09:34Z |
| publishDate | 2018-05-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-843e6e7b40c946a988e416fd87f7be582022-12-21T19:34:02ZengTaylor & Francis GroupOncoImmunology2162-402X2018-05-017510.1080/2162402X.2017.13898211389821Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironmentGabriela Vera-Lozada0Carolina Minnicelli1Priscilla Segges2Gustavo Stefanoff3Flavia Kristcevic4Joaquin Ezpeleta5Elizabeth Tapia6Gerald Niedobitek7Mário Henrique M. Barros8Rocio Hassan9Oncovirology Laboratory, Bone Marrow Transplantation Center (CEMO), Department of Clinical Analysis and Toxicology, Instituto Nacional de Câncer (INCA)Oncovirology Laboratory, Bone Marrow Transplantation Center (CEMO), Department of Clinical Analysis and Toxicology, Instituto Nacional de Câncer (INCA)Oncovirology Laboratory, Bone Marrow Transplantation Center (CEMO), Department of Clinical Analysis and Toxicology, Instituto Nacional de Câncer (INCA)Coordination of Clinical Research, INCACentro Internacional Franco Argentino de Ciencias de la Información y de Sistemas (CIFASIS), CONICETCentro Internacional Franco Argentino de Ciencias de la Información y de Sistemas (CIFASIS), CONICETCentro Internacional Franco Argentino de Ciencias de la Información y de Sistemas (CIFASIS), CONICETInstitute for Pathology, Unfallkrankenhaus BerlinInstitute for Pathology, Unfallkrankenhaus BerlinOncovirology Laboratory, Bone Marrow Transplantation Center (CEMO), Department of Clinical Analysis and Toxicology, Instituto Nacional de Câncer (INCA)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.http://dx.doi.org/10.1080/2162402X.2017.1389821chlsingle nucleotide polymorphisms (snp)survivaltumor microenvironmentmafmacrophages |
| spellingShingle | Gabriela Vera-Lozada Carolina Minnicelli Priscilla Segges Gustavo Stefanoff Flavia Kristcevic Joaquin Ezpeleta Elizabeth Tapia Gerald Niedobitek Mário Henrique M. Barros Rocio Hassan Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironment OncoImmunology chl single nucleotide polymorphisms (snp) survival tumor microenvironment maf macrophages |
| 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 |
| title_full | Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironment |
| title_fullStr | Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironment |
| title_full_unstemmed | Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironment |
| title_short | Interleukin 10 (IL10) proximal promoter polymorphisms beyond clinical response in classical Hodgkin lymphoma: Exploring the basis for the genetic control of the tumor microenvironment |
| title_sort | interleukin 10 il10 proximal promoter polymorphisms beyond clinical response in classical hodgkin lymphoma exploring the basis for the genetic control of the tumor microenvironment |
| topic | chl single nucleotide polymorphisms (snp) survival tumor microenvironment maf macrophages |
| url | http://dx.doi.org/10.1080/2162402X.2017.1389821 |
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