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The roles of Ptpn22 Ser452 phosphorylation in tumor-infiltrating CD8+ T cells from mouse

ABSTRACT: The roles of Ptpn22 Ser452 phosphorylation in tumor-infiltrating CD8+ T cells from mouse

PROVIDER: PRJNA1095827 | ENA |

REPOSITORIES: ENA

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The roles of Ptpn22 Ser452 phosphorylation in tumor-infiltrating CD8+ T cells from mouse

Project description:Protein Tyrosine Phosphatase Non-receptor type 22 (PTPN22) is encoded by a major autoimmunity gene and is a known inhibitor of T cell receptor (TCR) signaling for cancer immunotherapy. However, little is known about PTPN22 phosphorylation in tumor infiltrating T cells. Here we characterize a phosphorylation site at Ser452 situated in the interdomain of PTPN22, and its roles in altering T cell function and tumor growth. Tumor infiltrating CD8+ T cells from PepWT or PepS452A mice were collected and subjected to next-generation sequencing (NGS). The results revealed it differentially regulates the genes expression of metabolic process, cytokine prodcution and adaptive immunity etc. This study explores the function of a novel phosphorylation site of PTPN22 that is involved in complex regulation of CD8+ T cell activity, fuctions and tumor growth.

2025-04-02 | GSE263092 | GEO

A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling

Project description:Protein Tyrosine Phosphatase Non-receptor type 22 (PTPN22) is encoded by a major autoimmunity gene and is a known inhibitor of T cell receptor (TCR) signaling and drug target for cancer immunotherapy. However, little is known about PTPN22 post-translational regulation. Here we characterize a phosphorylation site at Ser325 situated C-terminal to the catalytic domain of PTPN22, and its roles in altering protein function. Signaling through the major TCR-dependent pathway under PTPN22 control was enhanced by CRISPR/Cas9 mediated suppression of Ser325 phosphorylation and inhibited by mimicking it via glutamic acid substitution. Next-generation sequencing (NGS) revealed it differentially regulates the expression of chemokines and T cell activation pathways. In conclusion, this study explores the function of a novel phosphorylation site of PTPN22 that is involved in complex regulation of TCR signaling .

2024-07-17 | GSE264373 | GEO

Expression data from FACS-sorted CD8+BTLA+ vs CD8+BTLA- Human Tumor-infiltrating Lymphocytes in Metastatic Melanoma

Project description:Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells. We used microarrays to detail the differences in the global programme of gene expression between CD8+BTLA+ vs CD8+BTLA- TILs in order to understand the molecular basis of the clinical association. TILs were isolated by enzymatically digest the melanoma tumor fragments obtained from Stage IIIc/IV melanoma patients at M.D. Anderson Cancer Center. The TILs were expanded with high-dose IL-2 for two weeks prior to sorting by FACS (fluoresecence-activated cell sorter) for CD8+BTLA+ and CD8+BTLA- susbets. RNA was extracted from each sorted subsets and hybridized on Affymetrix microarrays

2013-01-03 | E-GEOD-43260 | biostudies-arrayexpress

Adoptive Cell Therapy Using Cancer Specific CD8+ Tumor Infiltrating Lymphocytes in Adult Patients With Solid Tumors

Project description:The subject of this study is the adoptive transfer of selected autologous tumor infiltrating lymphocytes (TIL) after in vitro expansion for the treatment of solid tumor malignancies. The TIL selection process is based on evidence showing that CD8+ TIL which co-express both CD39 and CD103 harbor the bulk of tumor-reactivity and that the remaining CD8 TIL is mainly composed of non-tumor reactive bystander cells. All of the expanded TIL that are produced (1-40 billion are expected) will be delivered in the form of a cell suspension to the participants by intravenous infusion. It is proposed that these selected TIL will produce a more potent and efficacious treatment of late-stage cancer.

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ATACseq profiling of various TOX+ and TOX- tumor-infiltrating CD8 T cells

Project description:TOX is selectively expressed in tumor-infiltrating CD8 T cells however the role of TOX in peripheral CD8 T cells is not known. The goal of this study is to elucidate changes in chromatin accessibility determined by ATAC-seq between TOX-sufficient and TOX-deficient tumor infiltrating CD8 T cells isolated from murine tumors.

2019-06-24 | GSE126970 | GEO

Gene expression profile at single cell level of total tumor-infiltrating CD8+ T cells

Project description:Goblet cells are considered as a homogeneous population in total tumor-infiltrating CD8+ T cells. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of total tumor-infiltrating CD8+ T cells.

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Gene expression profiles of tumor-infiltrating CD8 T cells in hepatocellular carcinoma

Project description:We report the gene expression profiles of MACS-sorted tumor-infiltrating CD8 T cells in hepatocellular carcinoma.

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Effect of depletion of LRIG1 on polyclonal CD8+ tumor infiltrating T cells and Effect of depletion of LRIG1 on OT1 CD8+ tumor-infiltrating T cells

Project description:To investigate the function of LRIG11 in regulating the differentiation of polyclonal CD8 tumor infiltrating T cells during the response to B16melanoma. And, To investigate the function of LRIG1 in regulating the activaiton of ovalbumin specific OT1 CD8+ T cells during the response to B16 tumor stably expresss ovalbumin as surrogate tumor antigen.

2024-01-02 | GSE245841 | GEO

Bulk RNA-seq of Pglyrp1 KO Tumor Infiltrating CD8+ T cells

Project description:To characterize the role of Pglyrp1 in tumor immunity, we performed bulk RNA-seq for MC38-OVA tumor infiltrating CD8+ T cells from wild type and Pglyrp1-deficient mice.

2023-06-12 | GSE223872 | GEO

Chromatin accessibility analysis of tumor-infiltrating CD8+ T cells from tumor-bearing mice transferred Nrf2-deficient CD8+ T cells. [ATACseq]

Project description:To identify unique chromatin regions predicting the anti-tumor efficacy of Nrf2-deleted smart CD8+ T cell therapy, we performed an assay for transposase-accessible chromatin sequencing (ATAC-seq) using tumor-infiltrating CD8+ T cells from tumor-bearing mice transferred Nrf2-deficient CD8+ T cells. From the analysis of ATAC-seq data, we identified quantitatively distinct open regions of chromatin that distinguish Nrf2-deficient CD8+ T cells or WT CD8+ T cells.

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