TRAF6 Regulates the Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Tumor-Bearing Host

Song, Ge; Zhang, Yue; Tian, Jie; Ma, Jie; Yin, Kai; Xu, Huaxi; Wang, Shengjun

doi:10.3389/fimmu.2021.649020

Cited by 10 publications

(9 citation statements)

References 51 publications

(60 reference statements)

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“…Depletion of RNF43 E3 ligase remodeled the TIME and facilitated Kras-induced oncogenesis in pancreatic cancer ( 110 ). TRAF6 E3 ligase reshaped TME by increasing the immunosuppressive functions of MDSCs via targeting K63-linked ubiquitination and phosphorylation of STAT3 ( 111 ). Knockdown of E3 ubiquitin ligase Cbl-b increased CAR T-cell effects and blocked CD8+ T-cell exhaustion, upregulated the expression of IFN-γ and TNFα, and accelerated tumor cell killing ( 112 ).…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy

et al. 2023

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The tumor microenvironment (TME) is the tumor surrounding environment, which is critical for tumor development and progression. TME is also involved in clinical intervention and treatment outcomes. Modulation of TME is useful for improving therapy strategies. PD-L1 protein on tumor cells interacts with PD-1 protein on T cells, contributing to T cell dysfunction and exhaustion, blockage of the immune response. Evidence has demonstrated that the expression of PD-1/PD-L1 is associated with clinical response to anti-PD-1/PD-L1 therapy in cancer patients. It is important to discuss the regulatory machinery how PD-1/PD-L1 protein is finely regulated in tumor cells. In recent years, studies have demonstrated that PD-1/PD-L1 expression was governed by various E3 ubiquitin ligases in TME, contributing to resistance of anti-PD-1/PD-L1 therapy in human cancers. In this review, we will discuss the role and molecular mechanisms of E3 ligases-mediated regulation of PD-1 and PD-L1 in TME. Moreover, we will describe how E3 ligases-involved PD-1/PD-L1 regulation alters anti-PD-1/PD-L1 efficacy. Altogether, targeting E3 ubiquitin ligases to control the PD-1/PD-L1 protein levels could be a potential strategy to potentiate immunotherapeutic effects in cancer patients.

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Section: Discussion and Perspectivesmentioning

confidence: 99%

The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy

et al. 2023

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“…Nrdp1 mediates the ubiquitination of the transcription factor C/EBPβ at the K63 site, which promotes the activation of C/EBPβ and subsequently upregulates arginase 1 (Arg1) expression ( Ye et al, 2012 ). TRAF6 and arginase 1 are related, and they are expressed at high levels in myeloid-derived suppressor cells (MDSCs) ( Song et al, 2021 ). Ubc9-mediated SUMOylation of interferon regulatory factor 4 (IRF4) increases its nuclear localization and stability.…”

Section: Ubiquitination and Sumoylation In Amino Acid Metabolism In C...mentioning

confidence: 99%

Regulation of Glucose, Fatty Acid and Amino Acid Metabolism by Ubiquitination and SUMOylation for Cancer Progression

Zhu

Peng

et al. 2022

Front. Cell Dev. Biol.

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Ubiquitination and SUMOylation, which are posttranslational modifications, play prominent roles in regulating both protein expression and function in cells, as well as various cellular signal transduction pathways. Metabolic reprogramming often occurs in various diseases, especially cancer, which has become a new entry point for understanding cancer mechanisms and developing treatment methods. Ubiquitination or SUMOylation of protein substrates determines the fate of modified proteins. Through accurate and timely degradation and stabilization of the substrate, ubiquitination and SUMOylation widely control various crucial pathways and different proteins involved in cancer metabolic reprogramming. An understanding of the regulatory mechanisms of ubiquitination and SUMOylation of cell proteins may help us elucidate the molecular mechanism underlying cancer development and provide an important theory for new treatments. In this review, we summarize the processes of ubiquitination and SUMOylation and discuss how ubiquitination and SUMOylation affect cancer metabolism by regulating the key enzymes in the metabolic pathway, including glucose, lipid and amino acid metabolism, to finally reshape cancer metabolism.

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“…Thus, TRAF6 plays a critical role in regulating the function of MDSCs. Song et al ( 134 ) reported that TRAF6 was highly expressed in the MDSCs of patients with lung cancer and TRAF6 knockdown impaired the immunosuppressive effects of MDSCs in vitro and in Lewis xenograft mice.…”

Section: Roles Of Ubiquitination In Modulating the Crosstalk Between ...mentioning

confidence: 99%

Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review)

et al. 2022

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The interaction between a tumor and the tumor microenvironment (TME) plays a key role in tumorigenesis and tumor progression. Ubiquitination, a crucial post-translational modification for regulating protein degradation and turnover, plays a role in regulating the crosstalk between a tumor and the TME. Thus, identifying the roles of ubiquitination in the process may assist researchers to investigate the mechanisms underlying tumorigenesis and tumor progression. In the present review article, new insights into the substrates for ubiquitination that are involved in the regulation of hypoxic environments, angiogenesis, chronic inflammation-mediated tumor formation, and the function of cancer-associated fibroblasts and infiltrating immune cells (tumor-associated macrophages, T-cells, myeloid-derived suppressor cells, dendritic cells, and natural killer cells) are summarized. In addition, the potential targets of the ubiquitination proteasome system within the TME for cancer therapy and their therapeutic effects are reviewed and discussed.

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TRAF6 Regulates the Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Tumor-Bearing Host

Cited by 10 publications

References 51 publications

The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy

The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy

Regulation of Glucose, Fatty Acid and Amino Acid Metabolism by Ubiquitination and SUMOylation for Cancer Progression

Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review)

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