Regulation of Treg Cell Metabolism and Function in Non-Lymphoid Tissues

Yang, Kai

doi:10.3389/fimmu.2022.909705

Cited by 10 publications

(6 citation statements)

References 166 publications

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“…This implies that the CD70-CD27 axis is crucial in regulating Tregs. Treg is critical for immune tolerance and modulating immune responses to pathogens and tumors [32]. Tregs are an immunosuppressive subpopulation of CD4+ T cells characterized by the regulation of the transcription factor FoxP3, regulates Treg differentiation and development [33].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer

Kong

Xiong

2023

Funct Integr Genomics

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The immune checkpoint molecule CD70 and its receptor CD27 constitute the signal transduction axis, which is abnormally expressed in many solid tumors and is crucial for T cell co-stimulation and immune escape. Tumor cells regulate the expression of CD27 by expressing CD70 in tumor microenvironment and promote immune escape.The discovery of the immunosuppressive effect of the CD70-CD27 signaling axis on tumor cells introduces a new anti-tumor immunotherapy -CD70. Although current research evidence suggests a link between CD70 and tumors, no pan-cancer analysis is available. Using the Cancer Genome Atlas and Gene Expression Omnibus datasets, we rst explored the potential carcinogenic role of the CD70-CD27 signaling axis in human malignancies. CD70 expression is up-regulated in most cancers and has an obvious correlation with the prognosis of tumor patients. The expression of CD70 and CD27 is associated with the level of regulatory T cells (Tregs) in ltration. In addition, T cell receptor signaling pathways, PI3K-Akt, NF-κB, and TNF signaling pathways are also involved in CD70-mediated immune escape. CD70 mainly regulates tumor immune escape by regulating T cell-mediated tumor killing, while Tregs may be its main T cell subset. Our rst pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of the CD70-CD27 signaling axis in different tumors.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer

Kong

Xiong

2023

Funct Integr Genomics

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“…As expected, we found both CD4+ and CD8+ T-cells as well as Tregs ( Figure 6 ) infiltrating the tumors to varying degrees, depending on time and treatment. In many tumor environments regulatory cells and CD4+ T-cells would dominate the response and produce an immune tolerant microenvironment ( 53 ). In addition, check point inhibition alone has the potential to increase immune evasion through proliferation of Tregs in the tumor when no additional immune stimulation is present ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

Tumor growth inhibition and immune system activation following treatment with thorium-227 conjugates and PD-1 check-point inhibition in the MC-38 murine model

et al. 2022

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Targeted thorium-227 conjugates comprise the combination of a monoclonal antibody with specificity for a tumor cell antigen and a 3,2-HOPO chelator enabling complexation of thorium-227 (Th-227). The radiolabeled conjugate functions as an effective delivery system of alpha-particle radiation to the surface of the tumor cell inducing difficult to repair complex DNA damage and cell death. In addition, the mechanism of action of targeted alpha therapy (TAT) appears to involve a significant component linked to stimulation of the immune system. We report herein evidence of immune activation and long-lasting immune protection of a TAT in a syngeneic model using the MC-38 murine cell line. Firstly, MC-38 cells were irradiated ex vivo with the thorium labeled antibody before subcutaneous implantation into mice. These mice were then rechallenged with MC-38 cells contra-laterally. In the group receiving irradiated cells, 9 out of 10 animals had no measurable tumor growth compared to aggressive tumor growth in the control group. Secondly, in an efficacy study, 500 kBq/kg of thorium labeled antibody alone or in combination with PD-1 checkpoint inhibitor gave statistically significant tumor growth inhibition compared to vehicle control. Animals with no measurable tumors were once again rechallenged contra-laterally with MC-38 cells. The re-growth of tumors was significantly delayed (approx. 60 days) in the treatment group compared to age-matched controls (approx. 30 days) in the monotherapy group. Interestingly, in the TAT/ PD-1 combination group no re-growth was observed demonstrating the potential of combining a TAT with checkpoint inhibition therapy. Finally, tumors were excised from treated mice and analyzed by flow cytometry and immunohistochemistry (IHC). Analysis revealed significant infiltration of CD8+ T-cells and mature dendritic cells compared to vehicle controls. Together these results indicated that an ongoing immune response from treatment with alpha radiation could be enhanced by check-point inhibition.

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“…Moreover, the accumulation of VAT-Treg cells is dependent upon signaling from TCR, FOXP3, and IL-33, while IL-7 is necessary for the homeostasis and proper functioning of skin-Tregs. This figure adapted from Yang ( 118 ).…”

Section: Treg-based Therapies In Cancermentioning

confidence: 99%

Regulating the regulatory T cells as cell therapies in autoimmunity and cancer

Hosseinalizadeh,

Rabiee,

Eghbalifard

et al. 2023

Front. Med.

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Regulatory T cells (Tregs), possess a pivotal function in the maintenance of immune homeostasis. The dysregulated activity of Tregs has been associated with the onset of autoimmune diseases and cancer. Hence, Tregs are promising targets for interventions aimed at steering the immune response toward the desired path, either by augmenting the immune system to eliminate infected and cancerous cells or by dampening it to curtail the damage to self-tissues in autoimmune disorders. The activation of Tregs has been observed to have a potent immunosuppressive effect against T cells that respond to self-antigens, thus safeguarding our body against autoimmunity. Therefore, promoting Treg cell stability presents a promising strategy for preventing or managing chronic inflammation that results from various autoimmune diseases. On the other hand, Tregs have been found to be overactivated in several forms of cancer, and their role as immune response regulators with immunosuppressive properties poses a significant impediment to the successful implementation of cancer immunotherapy. However, the targeting of Tregs in a systemic manner may lead to the onset of severe inflammation and autoimmune toxicity. It is imperative to develop more selective methods for targeting the function of Tregs in tumors. In this review, our objective is to elucidate the function of Tregs in tumors and autoimmunity while also delving into numerous therapeutic strategies for reprogramming their function. Our focus is on reprogramming Tregs in a highly activated phenotype driven by the activation of key surface receptors and metabolic reprogramming. Furthermore, we examine Treg-based therapies in autoimmunity, with a specific emphasis on Chimeric Antigen Receptor (CAR)-Treg therapy and T-cell receptor (TCR)-Treg therapy. Finally, we discuss key challenges and the future steps in reprogramming Tregs that could lead to the development of novel and effective cancer immunotherapies.

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Regulation of Treg Cell Metabolism and Function in Non-Lymphoid Tissues

Cited by 10 publications

References 166 publications

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer

Tumor growth inhibition and immune system activation following treatment with thorium-227 conjugates and PD-1 check-point inhibition in the MC-38 murine model

Regulating the regulatory T cells as cell therapies in autoimmunity and cancer

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