ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemia
IntroductionB-cell acute lymphoblastic leukemia (B-ALL) in adults often presents a poor prognosis. ID1 and ID3 genes have been identified as predictors of poor response in Colombian adult B-ALL patients, contributing to cancer development. In various cancer models, these genes have been associated w...
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Frontiers Media S.A.
2024-11-01
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| author | Nathaly Poveda-Garavito Nathaly Poveda-Garavito Nathaly Poveda-Garavito Carlos A. Orozco Castaño Carlos A. Orozco Castaño Yulieth Torres-Llanos Yulieth Torres-Llanos Yulieth Torres-Llanos Nataly Cruz-Rodriguez Rafael Parra-Medina Rafael Parra-Medina Sandra Quijano Jovanny Zabaleta Alba Lucia Combita Alba Lucia Combita Alba Lucia Combita |
| author_facet | Nathaly Poveda-Garavito Nathaly Poveda-Garavito Nathaly Poveda-Garavito Carlos A. Orozco Castaño Carlos A. Orozco Castaño Yulieth Torres-Llanos Yulieth Torres-Llanos Yulieth Torres-Llanos Nataly Cruz-Rodriguez Rafael Parra-Medina Rafael Parra-Medina Sandra Quijano Jovanny Zabaleta Alba Lucia Combita Alba Lucia Combita Alba Lucia Combita |
| author_sort | Nathaly Poveda-Garavito |
| collection | DOAJ |
| description | IntroductionB-cell acute lymphoblastic leukemia (B-ALL) in adults often presents a poor prognosis. ID1 and ID3 genes have been identified as predictors of poor response in Colombian adult B-ALL patients, contributing to cancer development. In various cancer models, these genes have been associated with immune regulatory populations within the tumor immune microenvironment (TIME). B-ALL progression alters immune cell composition and the bone marrow (BM) microenvironment, impacting disease progression and therapy response. This study investigates the relationship between ID1 and ID3 expression, TIME dynamics, and immune evasion mechanisms in adult B-ALL patients. MethodsThis exploratory study analysed BM samples from 10 B-ALL adult patients diagnosed at the National Cancer Institute of Colombia. First, RT-qPCR was used to assess ID1 and ID3 expression in BM tumour cells. Flow cytometry characterised immune populations in the TIME. RNA-seq evaluated immune genes associatedwith B-ALL immune response, while xCell and CytoSig analysed TIME cell profiles and cytokines. Pathway analysis, gene ontology, and differential gene expression (DEGs) were examined, with functional enrichment analysis performed using KEGG ontology.ResultsPatients were divided into two groups based on ID1 and ID3 expression, namely basal and overexpression. A total of 94 differentially expressed genes were identified between these groups, with top overexpressed genes associated with neutrophil pathways. Gene set enrichment analysis revealed increased expression of genes associated with neutrophil degranulation, immune response-related neutrophil activation, and neutrophil-mediated immunity. These findings correlated with xCell data. Overexpression group showed significant differences in neutrophils, monocytes and CD4+ naive T cells compared to basal group patients. Microenvironment and immune scores were also significantly different, consistent with the flow cytometry results. Elevated cytokine levels associated with neutrophil activation supported these findings. Validation was performed using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) TCGA B-ALL cohorts.DiscussionThese findings highlight significant differences in ID1 and ID3 expression levels and their impact on TIME populations, particularly neutrophil-related pathways. The results suggest a potential role for ID1 and ID3 in immune evasion in adult B-ALL, mediated through neutrophil activation and immune regulation. |
| format | Article |
| id | doaj-art-b80bb8bfe9a7448093cc2f62439df86a |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-b80bb8bfe9a7448093cc2f62439df86a2024-11-29T05:10:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14739091473909ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemiaNathaly Poveda-Garavito0Nathaly Poveda-Garavito1Nathaly Poveda-Garavito2Carlos A. Orozco Castaño3Carlos A. Orozco Castaño4Yulieth Torres-Llanos5Yulieth Torres-Llanos6Yulieth Torres-Llanos7Nataly Cruz-Rodriguez8Rafael Parra-Medina9Rafael Parra-Medina10Sandra Quijano11Jovanny Zabaleta12Alba Lucia Combita13Alba Lucia Combita14Alba Lucia Combita15Grupo de Investigación en Biología del Cáncer – Instituto Nacional de Cancerología, Bogotá, ColombiaGrupo de Investigación Traslacional en Oncología – Instituto Nacional de Cancerología, Bogotá, ColombiaMaestría en Inmunología, Departamento de Microbiología – Universidad Nacional de Colombia, Bogotá, ColombiaGrupo de Investigación en Biología del Cáncer – Instituto Nacional de Cancerología, Bogotá, ColombiaGrupo de Investigación Traslacional en Oncología – Instituto Nacional de Cancerología, Bogotá, ColombiaGrupo de Investigación en Biología del Cáncer – Instituto Nacional de Cancerología, Bogotá, ColombiaGrupo de Investigación Traslacional en Oncología – Instituto Nacional de Cancerología, Bogotá, ColombiaLaboratorio clínico, Hospital Universitario San Ignacio, Bogotá, ColombiaStem Cell Program, Versiti Blood Research Institute, Milwaukee, WI, United StatesDepartamento de Patología, Instituto Nacional de Cancerología, Bogotá, ColombiaResearch Institute, Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá, ColombiaGrupo de Inmunobiología y Biología Celular, Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, ColombiaDepartment of Interdisciplinary Oncology, Louisiana State University Health Sciences Center, New Orleans, LA, United StatesGrupo de Investigación en Biología del Cáncer – Instituto Nacional de Cancerología, Bogotá, ColombiaGrupo de Investigación Traslacional en Oncología – Instituto Nacional de Cancerología, Bogotá, ColombiaMaestría en Inmunología, Departamento de Microbiología – Universidad Nacional de Colombia, Bogotá, ColombiaIntroductionB-cell acute lymphoblastic leukemia (B-ALL) in adults often presents a poor prognosis. ID1 and ID3 genes have been identified as predictors of poor response in Colombian adult B-ALL patients, contributing to cancer development. In various cancer models, these genes have been associated with immune regulatory populations within the tumor immune microenvironment (TIME). B-ALL progression alters immune cell composition and the bone marrow (BM) microenvironment, impacting disease progression and therapy response. This study investigates the relationship between ID1 and ID3 expression, TIME dynamics, and immune evasion mechanisms in adult B-ALL patients. MethodsThis exploratory study analysed BM samples from 10 B-ALL adult patients diagnosed at the National Cancer Institute of Colombia. First, RT-qPCR was used to assess ID1 and ID3 expression in BM tumour cells. Flow cytometry characterised immune populations in the TIME. RNA-seq evaluated immune genes associatedwith B-ALL immune response, while xCell and CytoSig analysed TIME cell profiles and cytokines. Pathway analysis, gene ontology, and differential gene expression (DEGs) were examined, with functional enrichment analysis performed using KEGG ontology.ResultsPatients were divided into two groups based on ID1 and ID3 expression, namely basal and overexpression. A total of 94 differentially expressed genes were identified between these groups, with top overexpressed genes associated with neutrophil pathways. Gene set enrichment analysis revealed increased expression of genes associated with neutrophil degranulation, immune response-related neutrophil activation, and neutrophil-mediated immunity. These findings correlated with xCell data. Overexpression group showed significant differences in neutrophils, monocytes and CD4+ naive T cells compared to basal group patients. Microenvironment and immune scores were also significantly different, consistent with the flow cytometry results. Elevated cytokine levels associated with neutrophil activation supported these findings. Validation was performed using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) TCGA B-ALL cohorts.DiscussionThese findings highlight significant differences in ID1 and ID3 expression levels and their impact on TIME populations, particularly neutrophil-related pathways. The results suggest a potential role for ID1 and ID3 in immune evasion in adult B-ALL, mediated through neutrophil activation and immune regulation.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1473909/fullB-cell acute lymphoblastic leukaemia (B-ALL)immune evasionimmune systemmicroenvironmentbone marrowimmunosurveillance |
| spellingShingle | Nathaly Poveda-Garavito Nathaly Poveda-Garavito Nathaly Poveda-Garavito Carlos A. Orozco Castaño Carlos A. Orozco Castaño Yulieth Torres-Llanos Yulieth Torres-Llanos Yulieth Torres-Llanos Nataly Cruz-Rodriguez Rafael Parra-Medina Rafael Parra-Medina Sandra Quijano Jovanny Zabaleta Alba Lucia Combita Alba Lucia Combita Alba Lucia Combita ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemia Frontiers in Immunology B-cell acute lymphoblastic leukaemia (B-ALL) immune evasion immune system microenvironment bone marrow immunosurveillance |
| title | ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemia |
| title_full | ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemia |
| title_fullStr | ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemia |
| title_full_unstemmed | ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemia |
| title_short | ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemia |
| title_sort | id1 and id3 functions in the modulation of the tumour immune microenvironment in adult patients with b cell acute lymphoblastic leukaemia |
| topic | B-cell acute lymphoblastic leukaemia (B-ALL) immune evasion immune system microenvironment bone marrow immunosurveillance |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1473909/full |
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