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Tumor-specific Th17-polarized cells eradicate large established melanoma

ABSTRACT: CD4+ T cells can differentiate into multiple effector subsets but the potential roles of these subsets in anti-tumor immunity have not been fully explored. We sought to study the impact of CD4+ T cell polarization on efficacy of tumor rejection in a model closely mimicking human disease where the target antigens are often non-mutated tissue differentiation self-antigens. We generated a new transgenic mouse model in which CD4+ T cells recognize a novel epitope in tyrosinase-related protein 1 (TRP-1), an antigen that is expressed by normal melanocytes and B16 murine melanoma. We found that cells could be robustly polarized into Th0, Th1 and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles as well as by surface markers, suggesting the potential for differential effector function in vivo. Contrary to the current view that Th1 cells play the most important role in tumor rejection, we found that Th17-polarized cells were superior in mediating destruction of advanced B16 melanoma. Unexpectedly, their therapeutic effect was critically dependent on IFN-γ production, while depletion of IL-17A and IL-23 had little impact. Taken together, these data indicate that the appropriate in vitro polarization of effector CD4+ T cells is decisive for the successful tumor eradication. This principle should be taken under consideration in the design of future clinical trials involving adoptive transfer-based immunotherapy of human malignancies. Two-condition experiment: RNA from TRP-1 transgenic mouse lymphocytes polarized to be either Th1 or Th17 were compared to cells polarized to be Th0. Keywords: Lymphocyte polarization comparison

ORGANISM(S): Mus musculus

PROVIDER: GSE10814 | GEO | 2008/03/15

SECONDARY ACCESSION(S): PRJNA107409

REPOSITORIES: GEO

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Tumor-specific Th17-polarized cells eradicate large established melanoma

Project description:CD4+ T cells can differentiate into multiple effector subsets but the potential roles of these subsets in anti-tumor immunity have not been fully explored. We sought to study the impact of CD4+ T cell polarization on efficacy of tumor rejection in a model closely mimicking human disease where the target antigens are often non-mutated tissue differentiation self-antigens. We generated a new transgenic mouse model in which CD4+ T cells recognize a novel epitope in tyrosinase-related protein 1 (TRP-1), an antigen that is expressed by normal melanocytes and B16 murine melanoma. We found that cells could be robustly polarized into Th0, Th1 and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles as well as by surface markers, suggesting the potential for differential effector function in vivo. Contrary to the current view that Th1 cells play the most important role in tumor rejection, we found that Th17-polarized cells were superior in mediating destruction of advanced B16 melanoma. Unexpectedly, their therapeutic effect was critically dependent on IFN-Î³ production, while depletion of IL-17A and IL-23 had little impact. Taken together, these data indicate that the appropriate in vitro polarization of effector CD4+ T cells is decisive for the successful tumor eradication. This principle should be taken under consideration in the design of future clinical trials involving adoptive transfer-based immunotherapy of human malignancies. Two-condition experiment: RNA from TRP-1 transgenic mouse lymphocytes polarized to be either Th1 or Th17 were compared to cells polarized to be Th0. Keywords: Lymphocyte polarization comparison Comparative analysis of gene expression changes observed when murine lymphocytes are differentially in vitro polarized .

2010-05-25 | E-GEOD-10814 | biostudies-arrayexpress

Gene expression data from polarized T helper cells isolated from mice with opticospinal (OSE) experimental autoimmune encephalomyelitis (EAE)

Project description:T cells from the spleen of a mixed-gender pool of four double-transgenic 2D2 (TCRMOG) x IgHMOG mice (OSE) mice, which spontaneously develop experimental autoimmune encephalomyelitis (EAE), were used to derive TH1- and TH17-polarized cells, as described in https://doi.org/10.1371/journal.pone.0015531. Here, expression was compared, first, between TH1 and naïve TH0 and, second, between TH17 and naïve TH0 cells.

2020-08-21 | E-MTAB-9133 | biostudies-arrayexpress

Project Title: Proteome analysis of CD4+ T cell subsets

Project description:Functionally distinct CD4+ helper T (Th) cell subsets, such as Th1, Th2, Th17, and regulatory T cells (Treg), play a pivotal role in the host-defense against pathogen invasion and the pathogenesis of inflammatory disorders. In this project, DIA-MS-based proteome analysis was performed on naïve CD4+ T, Th0, Th1, Th2, Th17 and iTreg cells using Q Exactive HF-X (Thermo Fisher Scientific) to search for proteins that differ among the cell subsets.

2023-01-04 | PXD036065 | JPOST Repository

Combinatorial flexibility of cytokine during Human T helper cells differentiation

Project description:Transcriptional analysis of human T cells differentiated in 4 T Helper context ( Th0, Th1, Th2 and Th17) in the presence or not of Interferon alpha We analyzed the transcriptomic profiles of 4 human naives T cells diferentiated in Th0, Th1, Th2 and Th17 in the presence or not of Interferon Alpha. Microarray analyses were performed in 2 time points : 1/ after Day 5 of polarization (= Day5); 2/ after Day 5+ four hours of re-stimulation (=Day 5+ 4H restim) in 3 different donors.

2014-05-29 | E-GEOD-54627 | biostudies-arrayexpress

Lipidomic analysis of CD4+ T-cell subsets (Th1,Th2,Th17 and iTreg cells) (part I)

Project description:Part 1/5: It includes lipidomic analysis of CD4+ T-cell subsets(Th1,Th2,Th17 and iTreg cells)and their paired controls(Th0 cells).

2021-01-28 | ST001676 | MetabolomicsWorkbench

P2X7 signaling drives Th1 cell differentiation through metabolic reprogramming for aerobic glycolysis

Project description:This study provides evidence on the molecular mechanisms by which P2RX7 signaling promotes Th1 cell differentiation. P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-polarized CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, ATP synthase blockade in vitro and the consequent inhibition of oxidative phosphorylation, which forces cells to use aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7. These data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 cell differentiation and suggest that ATP synthase inhibition is a fundamental mechanism by which P2X7 signaling induces the Th1 response.

2023-03-08 | PXD037754 | Pride

Gene expression profiling of human Th17 cell differentiation

Project description:The study aims at identifying transcriptional changes induced by in vitro polarization of human cord blood CD4+ cells towards Th17 subtype with combination of IL6, IL1b and TGFb by using timeseries data. In this study, we identified gene expression changes characterizing early stages of human Th17 cell differentiation program through genome-wide gene expression profiling. Primary T helper cells isolated from umbilical cord blood were used to construct detailed kinetic patterns of gene expression after initiation of Th17 differentiation with IL1b, IL6 and TGFb. The dataset described provides the starting point for defining the gene regulatory networks and identifying new candidates regulating the Th17 differentiation in human. Altogether 57 samples were analyzed representing 3 biological replicates of timeseries data (0, 0.5, 1, 2, 4, 6, 12, 24, 48 and 72 hours) of Th17 polarized cells and control Th0 cells

2012-05-03 | E-GEOD-35103 | biostudies-arrayexpress

Expression data for effector T cells

Project description:In this study, we examined differential gene expression in naïve human CD4+ T cells, as well as in effector Th1, Th17-negative and Th17-enriched CD4- T cell subsets. We observed a marked enrichment for increased gene expression in effector CD4+ T cells compared to naive CD4+ among immune-mediated disease oci genes. Within effector T cells, expression of disease-associated genes was increased in Th17-enriched compared to Th17-negative cells. We used microarray to examine the gene expresssion profile and level of human naïve, Th1 and effector T cell subsets. Human PBMCs were isolated and sorted to naïve, CD161-CCR6- and CD161+CCR6+ memory T cells. Naïve T cells were differentiatied to Th1 cells, and CD161-CCR6- and CD161+CCR6+ memory T cells were in vitro expanded for Th17-negative and Th17-enriched effector T cells. The gene profile was compared among naive, Th1, Th17-negative, and Th17-enriched cell subsets.

2012-05-12 | E-GEOD-32901 | biostudies-arrayexpress

Profiling of human CD4+ T subsets identifies a Th2-specific non-coding RNA GATA3-AS1

Project description:Host defense against diverse pathogens involves the recruitment and differentiation of CD4+ T effector subsets including T helper 1 (Th1), Th2, Th17 and induced regulatory T (Treg) cells. Surface phenotype studies have revealed subset-specific surface markers for the identification and purification of human primary CD4+ T effector subsets. In the present study, we aimed to characterize the mRNA and large intergenic non-coding RNA (lincRNA) expression differences between human primary CD4+ T effector subsets and identify potential subset-specific genes. To achieve this goal, mRNA and lincRNA microarray profiling of flow cytometry-sorted human primary Th1, Th2, Th17 and Treg cells was performed. Principal component and pathway analyses revealed subset-specific gene expression patterns. A Th2-specific lincRNA, GATA3-AS1, also termed FLJ45983, was identified in primary immune cells and tissues, as well as in in vitro polarized CD4+ T effector subsets. Further analysis showed that GATA3-AS1 was a potential diagnostic marker in allergy, a Th2-associated disease. This first systematic genome-wide analysis of gene expression differences between primary CD4+ T effector subsets may help to identify novel regulatory protein-coding genes and lincRNAs regulating CD4+ T cell subset differentiation, as well as potential diagnostic markers. As an example, we identified a GATA3-associated Th2-specific marker lincRNA GATA3-AS1. Gene expression microarray analysis of flow-cytometry sorted human primary naÃ¯ve CD4+ T cells, CD4+ T central memory cells, Th1, Th2, Th17 and Treg cells from buffy coat of four healthy controls Gene expression microarray analysis was performed using SurePrint G3 Human Gene Expression 8X60K microarray.

2013-06-01 | E-GEOD-43005 | biostudies-arrayexpress

Population RNA-seq of in vitro polarized CD4 T cells

Project description:To understand the molecular programs driving Th17 heterogeneity and CD4 T cell fate, we profiled in vitro polarized non-pathogenic Th17, pathogenic Th17, Th1, and Treg cells using RNA-seq.

2023-06-01 | GSE206304 | GEO

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