Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation

Kefaloyianni, Eirini

doi:10.1002/1873-3468.14305

Cited by 17 publications

(14 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An aspect of common gamma-chain cytokine biology that is outside the scope of this review, but could have important implications in cancer immunotherapy, is the soluble form of each cytokine receptor. The generation of soluble cytokine receptors and their ability to regulate the immune response has been comprehensively reviewed elsewhere ( 113 ). It is worth noting that while all cytokines reviewed in this manuscript are currently being tested in ongoing clinical trials ( Table 1 ), IL-4 and IL-9 also utilize the gamma-chain receptor subunit.…”

Section: Discussionmentioning

confidence: 99%

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

Wolfarth¹,

Dhar²,

Goon³

et al. 2022

Immune Netw

View full text Add to dashboard Cite

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short half-life of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

Wolfarth¹,

Dhar²,

Goon³

et al. 2022

Immune Netw

View full text Add to dashboard Cite

show abstract

“…The generation of soluble cytokine receptors has been extensively studied and multiple mechanisms are reported [39,40]. Generally, most cytokine receptors possess a transmembrane region, anchoring the receptor within the plasma membrane and allowing signal transduction.…”

Section: Generation Of the Soluble Il-2ramentioning

confidence: 99%

“…The second mechanism generates soluble cytokine receptors via alternatively processed mRNA and is referred to as alternative splicing. After the transcription, usually the exon encoding for the transmembrane region is spliced out, resulting in a shorter soluble version of the cytokine receptor, which is secreted similarly to other soluble proteins [39,40]. Of note, ectodomain shedding and alternative splicing are not exclusive, but both mechanisms can contribute to the generation of a specific soluble cytokine receptor.…”

Section: Generation Of the Soluble Il-2ramentioning

confidence: 99%

The soluble IL‐2 receptor α/CD25 as a modulator of IL‐2 function

Lokau,

Petasch,

Garbers

2023

Immunology

View full text Add to dashboard Cite

The pleiotropic cytokine interleukin‐2 (IL‐2) is an integral regulator of healthy and pathological immune responses, with the most important role in regulating the homeostasis of regulatory T cells. IL‐2 signalling involves three distinct receptors: The IL‐2 receptor α (IL‐2Rα/CD25), IL‐2Rβ, and IL‐2Rγ/γc. While IL‐2Rβ and γc are essential for signal transduction, IL‐2Rα regulates the affinity of the receptor complex towards IL‐2. A soluble form of the IL‐2Rα (sIL‐2Rα) is present in the blood of healthy individuals and increased under various pathological conditions. Although it is known that the sIL‐2Rα retains its ability to bind IL‐2, it is not fully understood how this molecule affects IL‐2 function and thus immune responses. Here, we summarize the current knowledge on the generation and function of the sIL‐2Rα. We describe the molecular mechanisms leading to sIL‐2Rα generation and discuss the different IL‐2 modulating functions that have been attributed to the sIL‐2Rα. Finally, we describe attempts to utilize the sIL‐2Rα as a therapeutic tool.

show abstract

“…There, they may trim cell surface receptors, e.g., cytokine receptors such as tumor necrosis factor receptor 1, interleukin 6 receptor alpha, and interleukin 1 receptor II ( 72 , 73 ) and plasma proteins ( 74 and references therein). Although soluble receptors do not transmit signals directly, they nevertheless can affect ligand binding and activation of membrane receptors and therefore indirectly modulate cellular signaling ( 75 ). Solubilized receptors can affect cytokine signaling far away from their site of origin ( 56 and references therein).…”

Section: Eraps In the Modulation Of Cytokine-mediated Signaling In Th...mentioning

confidence: 99%

To Be or Not to Be: The Case of Endoplasmic Reticulum Aminopeptidase 2

Kuśnierczyk

2022

Front. Immunol.

View full text Add to dashboard Cite

To be, or not to be, that is the question. (William Shakespeare, Hamlet)Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2, respectively) play a role in trimming peptides that are too long to be bound and presented by class I HLA (HLA-I) molecules to CD8+ T cells. They may also affect the HLA-I-presented peptide repertoire by overtrimming potential epitopes. Both enzymes may also be released from the cell to cleave cytokine receptors and regulate blood pressure. Both enzymes are polymorphic, which affects their expression, specificity, and activity, resulting in their role in diseases associated with HLA-I. In this brief review, we concentrate on ERAP2, less investigated because of its lack in laboratory mice and 25% of humans, as well as a lower polymorphism. ERAP2 was found to be associated with several diseases and to influence ERAP1 effects. It was discovered recently that the defective ERAP2 gene, not encoding functional aminopeptidase, may nevertheless, during viral infections, produce a truncated protein isoform of unknown function, possibly interfering with ERAP1 and full-length ERAP2 by heterodimer formation. The disease associations of ERAP2, alone or in combination with ERAP1, are reviewed.

show abstract

Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation

Cited by 17 publications

References 130 publications

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

The soluble IL‐2 receptor α/CD25 as a modulator of IL‐2 function

To Be or Not to Be: The Case of Endoplasmic Reticulum Aminopeptidase 2

Contact Info

Product

Resources

About