Mechanism of Action of IL-7 and Its Potential Applications and Limitations in Cancer Immunotherapy

Gao, Jianbao; Zhao, Li; Wan, Yisong Y.; Zhu, Bo

doi:10.3390/ijms160510267

Cited by 103 publications

(101 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The oncogenic role of TGF-β has also been reported and suspected to be a therapeutic target in advanced cancer [53]. Recent reports have designated USP15 as a “biological thermostat” of the TGF-β pathway, because it is capable of subtle modulation of the TGF-β activity (Figure 3) [35,54].…”

Section: Usp15 and Oncogenic Signalingmentioning

confidence: 99%

The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases

Chou

Chang

Korinek

et al. 2017

IJMS

View full text Add to dashboard Cite

Deubiquitinases (DUBs) play a critical role in ubiquitin-directed signaling by catalytically removing the ubiquitin from substrate proteins. Ubiquitin-specific protease 15 (USP15), a member of the largest subfamily of cysteine protease DUBs, contains two conservative cysteine (Cys) and histidine (His) boxes. USP15 harbors two zinc-binding motifs that are essential for recognition of poly-ubiquitin chains. USP15 is grouped into the same category with USP4 and USP11 due to high degree of homology in an N-terminal region consisting of domains present in ubiquitin-specific proteases (DUSP) domain and ubiquitin-like (UBL) domain. USP15 cooperates with COP9 signalosome complex (CSN) to maintain the stability of cullin-ring ligase (CRL) adaptor proteins by removing the conjugated ubiquitin chains from RBX1 subunit of CRL. USP15 is also implicated in the stabilization of the human papillomavirus type 16 E6 oncoprotein, adenomatous polyposis coli, and IκBα. Recently, reports have suggested that USP15 acts as a key regulator of TGF-β receptor-signaling pathways by deubiquitinating the TGF-β receptor itself and its downstream transducers receptor-regulated SMADs (R-SMADs), including SMAD1, SMAD2, and SMAD3, thus activating the TGF-β target genes. Although the importance of USP15 in pathologic processes remains ambiguous so far, in this review, we endeavor to summarize the literature regarding the relationship of the deubiquitinating action of USP15 with the proteins involved in the regulation of Parkinson’s disease, virus infection, and cancer-related signaling networks.

show abstract

Section: Usp15 and Oncogenic Signalingmentioning

confidence: 99%

The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases

Chou

Chang

Korinek

et al. 2017

IJMS

View full text Add to dashboard Cite

show abstract

“…This notion is supported by higher levels of expression of IL-7rα (CD127) ex vivo on NK cells from CR mice: IL-7 is a stromal cell-derived hematopoietic growth factor that is required for homeostatic proliferation and survival of NK cells (53, 66). However, previous observations suggest that CD127 + NK cell numbers are similar in control and CR mice at 6 months of age but that numbers of other NK cell subsets are lower (44).…”

Section: Discussionmentioning

confidence: 94%

Calorie Restriction Attenuates Terminal Differentiation of Immune Cells

et al. 2017

View full text Add to dashboard Cite

Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a−CD44lo cells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b−CD27+ cells and correspondingly lower proportions of highly differentiated CD11b+CD27−NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations.

show abstract

“…IL‐7, another common gamma γ c cytokine, is also considered for use in cancer and chronic viral infections, highlighting the potential in immunotherapies. This is particularly important in the carinogenic trematodes, S. haematobium, Opisthorchis viverrini and Clonorchis sinensis where one of the pathological manifestations of these infections is cancer in different organs (bladder, bile duct and liver) for which we currently do not have any therapeutic interventions beyond surgery.…”

Section: Modulating Ilc2 Responsesmentioning

confidence: 99%

Group 2 ILCs: A way of enhancing immune protection against human helminths?

Nausch

Mutapi

2017

Parasite Immunology

View full text Add to dashboard Cite

SummaryGroup 2 innate lymphoid cells (ILC2s) play crucial roles in type 2 immune responses associated with allergic and autoimmune diseases, viral and helminth infections and tissue homoeostasis. Experimental models show that in helminth infections ILC2s provide an early source of type 2 cytokines and therefore are essential for the induction of potentially protective type 2 responses. Much of our knowledge of ILC2s in helminth infections has come from experimental mouse models with very few studies analysing ILC2s in natural human infections. In attempts to harness knowledge from paradigms of the development of protective immunity in human helminth infections for vaccine development, the role of ILC2 cells could be pivotal. So far, potential vaccines against human helminth infections have failed to provide effective protection when evaluated in human studies. In addition to appropriate antigen selection, it is apparent that more detailed knowledge on mechanisms of induction and maintenance of protective immune responses is required. Therefore, there is need to understand how ILC2 cells induce type 2 responses and subsequently support the development of a protective immune response in the context of immunizations. Within this review, we summarize the current knowledge of the biology of ILC2s, discuss the importance of ILC2s in human helminth infections and explore how ILC2 responses could be boosted to efficiently induce protective immunity.

show abstract

Mechanism of Action of IL-7 and Its Potential Applications and Limitations in Cancer Immunotherapy

Cited by 103 publications

References 82 publications

The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases

The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases

Calorie Restriction Attenuates Terminal Differentiation of Immune Cells

Group 2 ILCs: A way of enhancing immune protection against human helminths?

Contact Info

Product

Resources

About