CD137 expression in cancer cells: regulation and significance

Glorieux, Christophe; Huang, Peng

doi:10.1186/s40880-019-0419-z

Cited by 13 publications

(13 citation statements)

References 12 publications

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“…While CD137 it is often associated with activation of T effector cells (40), recent clinical data revealed that CD8+ TILs expressing CD137 indicated a highly exhausted cell profile in hepatocellular carcinoma patients (41). In PDAC patient samples, tumor cells express CD137 through the activation of K-Ras and MAPK activation (39). In the present data set, CD137 was not associated with improved anti-tumor response.…”

Section: Discussioncontrasting

confidence: 51%

“…From the co-stimulatory perspective, CD137 was upregulated by both armed viruses. Nevertheless, the expression of CD137 expression in tumors is quite controversial (39,40). While CD137 it is often associated with activation of T effector cells (40), recent clinical data revealed that CD8+ TILs expressing CD137 indicated a highly exhausted cell profile in hepatocellular carcinoma patients (41).…”

Section: Discussionmentioning

confidence: 99%

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Oncolytic Adenovirus Coding for a Variant Interleukin 2 (vIL-2) Cytokine Re-Programs the Tumor Microenvironment and Confers Enhanced Tumor Control

et al. 2021

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The notion of developing variants of the classic interleukin 2 (IL-2) cytokine has emerged from the limitations observed with the systemic use of human IL-2 in the clinic: severe adverse events accompanied by low therapeutic response rate in treated patients. Modifications made in the IL-2 receptor-binding structure leads to preferential binding of IL-2 variant cytokine to receptors on effector anti-tumor lymphocytes over T regulatory (TReg) cells. Because of their inherent immunogenicity, oncolytic adenoviruses are useful for expression of immunomodulatory molecules in tumors, for induction of a pro-inflammatory state in the tumor microenvironment. In the present study, we constructed an adenovirus coding for an IL-2 variant (vIL-2) protein, Ad5/3-E2F-d24-vIL2. Functionality of the new virus was tested in vitro, and anti-tumor efficacy and mechanism of action studies were performed in immunocompetent hamsters bearing pancreatic tumors. Ad5/3-E2F-d24-vIL2 treatment elicited efficient anti-tumor response, with 62.5% monotherapy complete response. Moreover, it promoted substantial repression of genes associated with myeloid cells mediated immunosuppression (CD11b, ARG1, CD206). This was seen in conjunction with upregulation of genes associated with tumor-infiltrating lymphocyte (TIL) cytotoxicity (CD3G, SAP, PRF1, GZMM and GZMK). In summary, Ad5/3-E2F-d24-vIL2 demonstrates therapeutic potential by counteracting immunosuppression and in efficiently coordinating lymphocytes mediated anti-tumor response in immunosuppressive tumors. Thus, Ad5/3-E2F-d24-vIL2 is a promising candidate for translation into clinical trials in human immunosuppressive solid tumors.

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Oncolytic Adenovirus Coding for a Variant Interleukin 2 (vIL-2) Cytokine Re-Programs the Tumor Microenvironment and Confers Enhanced Tumor Control

et al. 2021

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“…TNFRSF9 is an important check point in cancer immunotherapy. However, as stated in previous studies, the significance of TNFRSF9 in cancer is not clear, but it was suggested to be immunosuppressive ( 43 – 46 ). Increased expression of TNFRSF9 was observed in platinum resistant ovarian tumors ( 27 , 47 , 48 ), which implies that this gene may promote tumor progression.…”

Section: Discussionmentioning

confidence: 88%

Immune-and Metabolism-Associated Molecular Classiﬁcation of Ovarian Cancer

Chen

Jiang

et al. 2022

Front. Oncol.

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Ovarian cancer (OV) is a complex gynecological disease, and its molecular characteristics are not clear. In this study, the molecular characteristics of OV subtypes based on metabolic genes were explored through the comprehensive analysis of genomic data. A set of transcriptome data of 2752 known metabolic genes was used as a seed for performing non negative matrix factorization (NMF) clustering. Three subtypes of OV (C1, C2 and C3) were found in analysis. The proportion of various immune cells in C1 was higher than that in C2 and C3 subtypes. The expression level of immune checkpoint genes TNFRSF9 in C1 was higher than that of other subtypes. The activation scores of cell cycle, RTK-RAS, Wnt and angiogenesis pathway and ESTIMATE immune scores in C1 group were higher than those in C2 and C3 groups. In the validation set, grade was significantly correlated with OV subtype C1. Functional analysis showed that the extracellular matrix related items in C1 subtype were significantly different from other subtypes. Drug sensitivity analysis showed that C2 subtype was more sensitive to immunotherapy. Survival analysis of differential genes showed that the expression of PXDN and CXCL11 was significantly correlated with survival. The results of tissue microarray immunohistochemistry showed that the expression of PXDN was significantly correlated with tumor size and pathological grade. Based on the genomics of metabolic genes, a new OV typing method was developed, which improved our understanding of the molecular characteristics of human OV.

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“…The T-cell costimulatory receptor TNFRSF9 is known as a novel target for immunotherapy [123][124][125]. TNFRSF9 is expressed on the surface of certain immune cells such as activated T cells and interacts with its ligand in activated antigen-presenting cells, leading to the activation of immunity against cancer [126]. DNA hypermethylation at the TNFRSF9 promoter site is associated with a reduced TNFRSF9 mRNA expression and unfavorable clinical behavior during anti-PD-1 antibody treatment [127], suggesting that the tumor might drive another advantageous strategy against the anti-tumor immune response during anti-PD-1 antibody treatment.…”

Section: Dna Hypermethylation In Tnfrsf9 During Anti-pd-1 Treatmentmentioning

confidence: 99%

Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma

Nanamori

Sawada

2022

IJMS

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Malignant melanoma is one of the representative skin cancers with unfavorable clinical behavior. Immunotherapy is currently used for the treatment, and it dramatically improves clinical outcomes in patients with advanced malignant melanoma. On the other hand, not all these patients can obtain therapeutic efficacy. To overcome this limitation of current immunotherapy, epigenetic modification is a highlighted issue for clinicians. Epigenetic modification is involved in various physiological and pathological conditions in the skin. Recent studies identified that skin cancer, especially malignant melanoma, has advantages in tumor development, indicating that epigenetic manipulation for regulation of gene expression in the tumor can be expected to result in additional therapeutic efficacy during immunotherapy. In this review, we focus on the detailed molecular mechanism of epigenetic modification in immunotherapy, especially anti-PD-1/PD-L1 antibody treatment for malignant melanoma.

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CD137 expression in cancer cells: regulation and significance

Cited by 13 publications

References 12 publications

Oncolytic Adenovirus Coding for a Variant Interleukin 2 (vIL-2) Cytokine Re-Programs the Tumor Microenvironment and Confers Enhanced Tumor Control

Oncolytic Adenovirus Coding for a Variant Interleukin 2 (vIL-2) Cytokine Re-Programs the Tumor Microenvironment and Confers Enhanced Tumor Control

Immune-and Metabolism-Associated Molecular Classiﬁcation of Ovarian Cancer

Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma

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