Prostaglandin E2 Selectively Inhibits Human CD4+ T Cells Secreting Low Amounts of Both IL-2 and IL-4

He, Xing; Stuart, J.

doi:10.4049/jimmunol.163.11.6173

Cited by 24 publications

(3 citation statements)

References 34 publications

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“…Consistent in many studies [20,23,41,67], KEAP1 mutations in lung cancer result in T-cell suppression that promotes immune escape and cancer progression, a finding we also observed. Our data expand on the causes of T-cell suppression as we have further identified an increase in immunosuppressive markers expressed on KEAP1-mutant cancer cells that inhibit the T-cell response (PD-L1 [45], CD80/CD86 [46,47], and CD155 [49,50]).…”

Section: Discussionsupporting

confidence: 92%

“…An excerpt from the MIF-Regulation of Innate Immunity Pathway is shown in Figure 7 c. QIAGEN IPA predicts strong upregulation of this section of the pathway, implying increased prostaglandin production. Notably, high levels of prostaglandin are associated with T-cell suppression [ 65 , 66 , 67 ] and polarization to an M2-like macrophage phenotype [ 68 , 69 ]. We verified increased COX-2 protein level in the KEAP1 KO cell lines ( Figure 7 d), which was elevated by 2–3-fold ( Figure 7 e), but not significantly altered in the NRF2 KO.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to differential regulation of cytokines, RNA sequencing of the cancer lines suggests a robust increase in prostaglandin synthesis pathways that could further suppress T-cell responses [ 65 , 66 , 67 ]. Prostaglandins are known immunomodulators released by various cancer types [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

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KEAP1-Mutant Lung Cancers Weaken Anti-Tumor Immunity and Promote an M2-like Macrophage Phenotype

Occhiuto,

Liby

2024

IJMS

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Considerable advances have been made in lung cancer therapies, but there is still an unmet clinical need to improve survival for lung cancer patients. Immunotherapies have improved survival, although only 20–30% of patients respond to these treatments. Interestingly, cancers with mutations in Kelch-like ECH-associated protein 1 (KEAP1), the negative regulator of the nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, are resistant to immune checkpoint inhibition and correlate with decreased lymphoid cell infiltration. NRF2 is known for promoting an anti-inflammatory phenotype when activated in immune cells, but the study of NRF2 activation in cancer cells has not been adequately assessed. The objective of this study was to determine how lung cancer cells with constitutive NRF2 activity interact with the immune microenvironment to promote cancer progression. To assess, we generated CRISPR-edited mouse lung cancer cell lines by knocking out the KEAP1 or NFE2L2 genes and utilized a publicly available single-cell dataset through the Gene Expression Omnibus to investigate tumor/immune cell interactions. We show here that KEAP1-mutant cancers promote immunosuppression of the tumor microenvironment. Our data suggest KEAP1 deletion is sufficient to alter the secretion of cytokines, increase expression of immune checkpoint markers on cancer cells, and alter recruitment and differential polarization of immunosuppressive macrophages that ultimately lead to T-cell suppression.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

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KEAP1-Mutant Lung Cancers Weaken Anti-Tumor Immunity and Promote an M2-like Macrophage Phenotype

Occhiuto,

Liby

2024

IJMS

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The intestinal mucosa as a target for dietary polyunsaturated fatty acids

Donnet-Hughes

Schiffrin

Turini

2001

Lipids

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Several studies have reported beneficial effects of dietary polyunsaturated fatty acids (PUFA) on various aspects of both human and animal health, and particular reference has been made to their effects on systemic immune responses. Both immune stimulation and immune suppression have been reported, with the outcome dependent on the type of PUFA, the target cell, as well as the immune competence of the cells before exposure. The systemic and the mucosal immune systems are discrete entities, which have evolved specific approaches in the defense of the host. The latter comprises several interconnected tissues, which communicate with one another through the action of soluble mediators and the trafficking of cellular components. After the oral mucosa, the intestinal epithelium and its associated gut-associated lymphoid tissue are the primary targets of dietary components. Absorption of dietary PUFA and its incorporation into intestinal tissues has been well studied, but the consequences of these events in relation to local immune responses have received little attention. This article describes some of the immune mechanisms operating at this barrier and, where possible, pinpoints areas for which a modulatory role for PUFA has already been demonstrated. Although not an exhaustive treatise of the subject, it is hoped that this review will foster research into the specific interaction between dietary PUFA and cell populations comprising the intestinal barrier.

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Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

et al. 2016

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Mesenchymal stem cells (MSCs) are a group of fibroblast-like multipotent mesenchymal stromal cells that have the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. Recent studies have demonstrated that MSCs possess a unique ability to exert suppressive and regulatory effects on both adaptive and innate immunity in an autologous and allogeneic manner. A vital step in stem cell transplantation is overcoming the potential graft-versus-host disease, which is a limiting factor to transplantation success. Given that MSCs attain powerful differentiation capabilities and also present immunosuppressive properties, which enable them to survive host immune rejection, MSCs are of great interest. Due to their ability to differentiate into different cell types and to suppress and modulate the immune system, MSCs are being developed for treating a plethora of diseases, including immune disorders. Moreover, in recent years, MSCs have been genetically engineered to treat and sometimes even cure some diseases, and the use of MSCs for cell therapy presents new perspectives for overcoming tissue rejection. In this review, we discuss the potential extrinsic and intrinsic mechanisms that underlie MSCs’ unique ability to modulate inflammation, and both innate and adaptive immunity.

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Prostaglandin E2 Selectively Inhibits Human CD4+ T Cells Secreting Low Amounts of Both IL-2 and IL-4

Cited by 24 publications

References 34 publications

KEAP1-Mutant Lung Cancers Weaken Anti-Tumor Immunity and Promote an M2-like Macrophage Phenotype

KEAP1-Mutant Lung Cancers Weaken Anti-Tumor Immunity and Promote an M2-like Macrophage Phenotype

The intestinal mucosa as a target for dietary polyunsaturated fatty acids

Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

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