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Gene expression patterns of tumor-infiltrating CD8 T cells according to the CD137 expression in human metastatic ovarian cancer

ABSTRACT: Gene expression patterns of tumor-infiltrating CD8 T cells according to the CD137 expression in human metastatic ovarian cancer

PROVIDER: PRJNA631736 | ENA |

REPOSITORIES: ENA

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Gene expression patterns of tumor-infiltrating CD8 T cells according to the CD137 expression in human metastatic ovarian cancer

Project description:We report the differences of gene expression pattern of tumor-infiltrating CD8 T cells between CD137 expressing cells and CD137 non-expressing cells in human metastatic ovarian cancer. Samples are obtained from 3 ovarian cancer patients, and we sorted CD137 expressing cells and CD137 non-expressing cells in CD39 expressing CD8 T cells for RNA sequencing. We found that even though the CD39 expression and PD-1 expression levels are similar, CD137 expressing cells showed more activated and less exhausted phenotypes than CD137 non-expressing cells.

2020-05-12 | GSE150301 | GEO

Single cell Transcriptomic analysis of CD8+ T cells treated with anti-CD137 agonists within VK12653 Multiple Myeloma bone marrow microenvironment .

Project description:We report the single cell RNA sequencing of mouse CD8+ T cells infiltrating VK12653 Multiple Myeloma lesions upon treatment with anti-CD137 agonists .

2023-06-30 | GSE205702 | GEO

CD137-CIS IO

Project description:CD137 cis-costimulation is superior to trans-costimulation at inducing transcriptomic differences in T-cell proliferation and DNA repair programs We used microarrays to detail differentially expressed genes of cis- and trans CD137-costimulated CD8 T cells with respect to CD3-TCR stimulation

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Project description:CD137-CIS IO

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Epithelial Ovarian Cancer is infiltrated by activated effector T cells co-expressing CD39, PD-1, TIM-3, CD137 and interacting with cancer cells and myeloid cells

Project description:Introduction: Despite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity. Methods: In this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs). Results: Activated T cells showing features of partial exhaustion with a CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ signature. Conclusions: These data demonstrate that EOC is enriched in CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches

2023-10-02 | GSE243751 | GEO

Effect of CD137 (4-1BB) triggering on human monocytes

Project description:The cell surface glycoprotein CD137, which is also known as 4-1BB, belongs to the group of co-stimulatory immune receptors and is a member of the TNF receptor superfamily (TNFRSF). It is preferentially found on activated T-cells and regulatory T-cells. In T-cells, CD137-crosslinking delivers a potent co-stimulatory signal as it promotes T-cell proliferation, formation of memory cells and enhances survival. Despite numerous studies investigating the effects of co-stimulatory CD137 in T-cells, little is known regarding the role of CD137 in human monocytes/macrophages. To investigate the effect of CD137 triggering on human monocytes, monocytes were isolated and treated with an agonistic CD137 mAb and subsequently analyzed by RNA-seq.

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Profiling of tumor-infiltrating CD8 T cells according to their expression status of CD39

Project description:Profiling of tumor-infiltrating CD8 T cells according to their expression status of CD39

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CD137 costimulation counteracts TGFβ inhibition of NK cell anti-tumor function and promotes the acquisition of tissue-resident Th9-like properties [2 treatments]

Project description:Enhancing NK cell-based cancer immunotherapy by overcoming immunosuppression is an unmet goal. Here, we demonstrate the ability of the anti-CD137 agonist urelumab for overcoming TGF-β-mediated inhibition of human NK-cell proliferation and sustained anti-tumor function. Transcriptomic, immunophenotypic and functional analyses evidenced that CD137 costimulation modified the transcriptional program induced by TGF-β on activated NK cells by limiting SMAD4-dependent inhibition of pro-proliferative (CD25, cMyc), activating (NKG2D, CD16) and effector (Granzyme B, IFNγ) molecules while maintaining SMAD4-independent acquisition of tumor-retention features (CXCR3, CD103). Activated NK cells cultured in the presence of TGF-β1 and CD137 agonist showed preserved antibody-dependent cytotoxicity against cancer cells, recovered CCL5 and IFNγ secretion and gained the capacity for producing IL-9 upon restimulation. Treatment of breast tumor-derived multicellular cultures with trastuzumab and urelumab recapitulated CD137 induction and fostered tumor-infiltrating CD16+ NK cell persistence. Our data reveals CD137 as a targetable checkpoint for overturning TGF-β constrains on NK cell anti-tumor responses

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CD137 costimulation counteracts TGFβ inhibition of NK cell anti-tumor function and promotes the acquisition of tissue-resident Th9-like properties [4 treatments]

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Profiling of lung tumor-infiltrating CD8 T cells according to their expression status of CD39

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