Tumor microenvironment impairs Th1 cell differentiation through alternative splicing modifications
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA556640 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9833170_1.fastq.gz | Fastqsanger.gz | |||
| SRR9833170_2.fastq.gz | Fastqsanger.gz | |||
| SRR9833180_1.fastq.gz | Fastqsanger.gz | |||
| SRR9833180_2.fastq.gz | Fastqsanger.gz | |||
| SRR9833190_1.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2021-04-27 | GSE134855 | GEO
Project description:It is now clearly established that immune system can affect cancer response to therapy. However, the influence of tumor microenvironment on immune cells is not completely understood. In this respect, alternative splicing is increasingly described to affect immune system biology. Here, we showed that tumor microenvironment, by increasing alternative splicing events, induced the expression of an alternative isoform of the IRF1 transcription factor in Th1 cells. Furthermore, we also shown, in both mice and humans, that IRF1 alternative isoform alters IRF1 full form transcriptional activity on Il12rb1 promotor, resulting in decreased IFN-? secretion in Th1 cells. Thus, IRF1-short isoform increases in tumor microenvironment and to prevent this isoform appearance could potentiate Th1 cell antitumor effect.
2021-04-27 | GSE134853 | GEO
Project description:Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. Here, we demonstrate a direct role for histone modifications in alternative splicing. We find distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. The mechanism for histone-mediated splice site selection involves a histone mark which is read by a chromatin protein, which in turn recruits a splicing regulator. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery. To obtain an estimate of how many PTB-dependent alternative splicing events are regulated by SET2/MRG15-mediated recruitment of PTB, we carried out a genomewide comparative analysis of alternative splicing in hMSC cells depleted of either SETD2, MRG15 or PTB using specific siRNAs, or mock-depleted using a control siRNA.
2010-02-10 | E-GEOD-19373 | biostudies-arrayexpress
Project description:Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. Here, we demonstrate a direct role for histone modifications in alternative splicing. We find distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. The mechanism for histone-mediated splice site selection involves a histone mark which is read by a chromatin protein, which in turn recruits a splicing regulator. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery.
2010-02-10 | GSE19373 | GEO
Project description:Transcriptional modifications driven by STING activation in polarizing TH1 and Th9 cells
| PRJNA613701 | ENA
Project description:T helper cell activation is highly regulated to ensure proper immune responses while avoiding autoimmune reactions. Cell functions are determined by regulation of various levels of gene expression including posttranslational modifications of proteins. Protein prenylation is a posttranslational modification, where either a farnesyl- or a geranylgeranyl residue is added to a protein. It was shown to play a role in the differentiation and activation of various T cell populations, including Th1 cells. However, it is largely unknown which proteins are prenylated in Th1 cells and what the effect of farnesyl transferase inhibitor treatment, which blocks farnesylation of proteins, on protein prenylation is in this context. Here, using mass spectrometry, we show the identification of farnesylated proteins in human Th1 cells. This approach additionally uncovered the farnesylation of proteins, not yet known to be prenylated. These data provide valuable insights into novel aspects of protein prenylation in Th1 cell activation and deepen our understanding of the effects of farnesyl transferase inhibitor treatment on the human immune system.
2025-01-18 | MSV000096890 | MassIVE
Project description:T helper cell activation is highly regulated to ensure proper immune responses while avoiding autoimmune reactions. Cell functions are determined by regulation of various levels of gene expression including posttranslational modifications of proteins. Protein prenylation is a posttranslational modification, which can be influenced by statin treatment and was shown to play a role in the differentiation and activation of various T cell populations, including Th1 cells. However, it is largely unknown which proteins are prenylated in Th1 cells and what the effect of statin treatment on protein prenylation is in this context. Here, using mass spectrometry, we show the comprehensive identification of prenylated proteins in human Th1 cells including changes during their activation, before analyzing the effect of statin treatment on this process. This approach additionally uncovered the prenylation of proteins, not yet known to be prenylated, including so far unknown motifs. These data provide valuable insights into novel aspects of protein prenylation in Th1 cell activation and deepen our understanding of the intended or unintended effects of statin treatment on the human immune system.
2024-08-12 | MSV000095575 | MassIVE
Project description:Overcoming immunosuppression in tumor microenvironment (TME) is fundamental to the development of novel cancer immunotherapies. Herein, we revealed an unrecognized role of IL-16 in shaping anti-tumor immunity. Compared with healthy subjects, cancer patients had impaired production of IL-16, which was correlated with inferior patient prognosis. In multiple murine cancer models, IL-16 administration augmented the anti-tumor immune responses and thus restrained tumor growth. Mechanistically, IL-16 potentiated the polarization of T helper 1 (Th1) cells and the production of their effector cytokine IFN-γ, Mechanistically, IL-16 blocked glutamine catabolism by downregulating glutaminase (GLS) expression in CD4+ T cells. The IL-16-established Th1 tumor microenvironment further increased the expression of CXCR3 ligands in tumor-associated macrophages, which improved the therapeutic efficacy of immune checkpoint blockade (ICB). In cancer patients who received anti-PD1 therapy, high IL-16 levels correlated with better responsiveness. Finally, we found that the impaired production of histamine by mast cells was a causative factor for IL-16 downregulation in TME. Thus, IL-16 administration may serve as a potential approach to augment anti-tumor immunity, and also improve the outcome of ICB therapy in cancer patients. Collectively, we provided new insights into the biological function of IL-16 and thus highlighted its potential clinical value in cancer immunotherapy.
2025-01-20 | GSE247579 | GEO
Project description:Immune stimulation contributes to lenalidomide’s anti-tumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T-cell function in vitro. Whether T-cell activation is required for clinical response to lenalidomide remains unclear. Here we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with anti-tumor response. Within days of starting lenalidomide, CD3+ cells increased in the tumor microenvironment and showed Th1-type polarization. Gene expression profiling of pre-treatment and on-treatment lymph node biopsies revealed upregulation of IFN and many of its target genes in response to lenalidomide. The IFNγ-mediated Th1 response was limited to patients achieving a clinical response defined by a reduction in lymphadenopathy. Deep sequencing of T-cell receptor genes revealed decreasing diversity of the T-cell repertoire and an expansion of select clonotypes in responders. To validate our observations, we stimulated T cells and CLL cells with lenalidomide in culture and detected lenalidomide-dependent increases in T-cell proliferation. Taken together, our data demonstrate that lenalidomide induced Th1 immunity in the lymph node that is associated with clinical response.
2018-07-25 | GSE112953 | GEO
Project description:Overcoming immunosuppression in tumor microenvironment (TME) is crucial for the development of novel cancer immunotherapies. In this study, we revealed a previously unrecognized role of IL-16 in shaping anti-tumor immunity. Compared to healthy individuals, cancer patients exhibited impaired production of IL-16, which was associated with inferior patient prognosis. In multiple murine cancer models, IL-16 administration augmented the anti-tumor immune responses and thus restrained tumor growth. Further investigation uncovered that IL-16 potentiated the polarization of T helper 1 (Th1) cells and the production of their effector cytokine IFN-γ. Mechanistically, IL-16 inhibited glutamine catabolism by downregulating the expression of glutaminase (GLS) in CD4+ T cells. The establishment of IL-16-dependent Th1 tumor microenvironment further increased the expression of CXCR3 ligands in tumor-associated macrophages (TAMs), thereby improving the therapeutic effectiveness of immune checkpoint blockade (ICB). In cancer patients who received anti-PD1 therapy, higher levels of IL-16 were correlated with better responsiveness. Finally, we found that the impaired production of histamine by mast cells was a contributing factor to the downregulation of IL-16 in TME. Therefore, IL-16 could potentially be utilized as a therapeutic approach to augment anti-tumor immunity, and improve the outcome of ICB therapy in cancer patients. Collectively, our research provided new insights into the biological function of IL-16, emphasizing its potential clinical significance in cancer immunotherapy.
2025-01-20 | GSE254991 | GEO