Immunotherapy of prostate cancer: identification of new treatments and targets for therapy, and role of WAP domain-containing proteins

2011 ◽  
Vol 39 (5) ◽  
pp. 1433-1436 ◽  
Author(s):  
Christine Galustian ◽  
Annapurna Vyakarnam ◽  
Oussama Elhage ◽  
Oliver Hickman ◽  
Prokar Dasgupta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Effector Cells ◽  
Stage Disease ◽  
Dendritic Cell Vaccines ◽  
Lymphocytic Infiltrates ◽  
New Treatments

Prostate adenocarcinoma is present in over 80% of men over the age of 80 and is by far the most common cancer of men. Although radical prostatectomy is curative in early disease, the risks of incontinence and impotence can affect the quality of life of patients. Early intervention with localized immunotherapy represents a potential solution as lymphocyte infiltration does occur in prostate cancer lesions, and immunotherapy with dendritic cell vaccines can significantly increase survival in late stage disease. However, lymphocytic infiltrates in the cancerous prostates have an anergic character arising from the suppressive effects of the microenvironment resulting from a conversion of effector cells into regulatory T-cells. Although TGFβ (transforming growth factor β) and IL-10 (interleukin-10) are known to be strong suppressor molecules associated with prostate cancer, they are among many possible suppressive factors. We discuss the possible role of alternative suppressor molecules, including the WAP (whey acidic protein) homologue ps20 that is expressed on prostate stroma and other WAP domain-containing proteins in the immunosuppressive prostate cancer milieu and discuss novel immunotherapeutic strategies to combat this disease.

scholarly journals Role of Transforming Growth Factor-β in Immunotherapy of Prostate Cancer

2007 ◽  
pp. 165-174 ◽  
Author(s):  
Chung Lee ◽  
Ali Shah ◽  
Victoria Liu ◽  
Irwin Park ◽  
Larry Wong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Metabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokines

1998 ◽  
Vol 330 (3) ◽  
pp. 1405-1409 ◽  
Author(s):  
Magdalena SASTRE ◽  
Elena GALEA ◽  
Douglas FEINSTEIN ◽  
J. Donald REIS ◽  
Soundararajan REGUNATHAN
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Arginine Decarboxylase ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Metabolic Route ◽  
Mammalian Tissues ◽  
Contrast Exposure ◽  
Oxide Synthase

Agmatine is an amine derived from the decarboxylation of arginine by arginine decarboxylase (ADC) and metabolized to putrescine by agmatinase. While prevalent in bacteria and plants, agmatine and its metabolic enzymes have been recently identified in mammalian tissues. In the present study we sought to determine: (a) whether macrophages (cell line RAW 264.7) express ADC and agmatinase, and (b) if the enzymes are regulated by lipopolysaccharide (LPS), and/or by the inhibitory cytokines transforming growth factor-β (TGF-β), interleukin-10 (IL-10) and interleukin-4 (IL-4). LPS induced a dose-dependent stimulation of agmatinase, while it decreased ADC, the effect in both cases being maximum at 20 h. As expected, LPS dose-dependently stimulated the inducible nitric oxide synthase activity (iNOS). A strong correlation was observed between the effects of LPS on the agmatine-related enzymes and iNOS. By contrast, exposure to IL-10 and TGF-β caused a reduction in ADC and agmatinase, whereas IL-4 was ineffective on ADC, but reverted the LPS-induced increase of agmatinase. We conclude that the agmatine pathway may be an alternative metabolic route for arginine in macrophages, suggesting a regulatory role of agmatine during inflammation.

scholarly journals Polymorphisms of Tumor Necrosis Factor-α, Transforming Growth Factor-β, and Interleukin-10 in Asthma Associated with Olive Pollen Sensitization

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Blanca Cárdaba ◽  
David Calzada ◽  
Selene Baos ◽  
Miriam Aguerri ◽  
Joaquín Quiralte ◽  
...  
Keyword(s):  
Protective Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Pollen Allergens ◽  
Allelic Discrimination ◽  
Factor Α ◽  
Olive Pollen ◽  
Necrosis Factor

Sensitization to specific olive pollen-allergens (Ole e 2 and 10) has been correlated with a clinical pattern of asthma. This study analyzes the association between several polymorphims ofTNFA(G-308A,C-857T, andC-1031T),IL10(C-571AandA-1117G), andTGFB(C-509-T) and these sensitizations. These polymorphisms were genotyped by allelic discrimination, in olive pollen-allergic patients (phenotyped for specific Ole e 2 and 10 sensitizations) and healthy controls. Levels of serum-soluble cytokines were correlated with specific genotypes and clinical phenotypes. The results showed that heterozygousTGFB C-509Tgenotype, besides having the lowest sera TGF- levels, was significantly increased in olive pollen-allergic patients compared with controls. According specific sensitizations,CCgenotype ofIL10 C-571Acould be a protective factor for Ole e 2 sensitization and mainly for asthmatic Ole e 2 sensitized patients compared with asthmatic non-Ole e 2 sensitized patients (OR: 0.26,P=0.008). In contrast, heterozygousCAgenotype was increased in Ole e 2 asthmatic subjects compared to asthmatic non-Ole e 2 sensitized patients. Lastly, heterozygousTNFA G-308Agenotype was associated with Ole e 10 sensitization (OR: 2.5,P=0.04). In conclusion, these results suggest a role of TGF-β1 in olive-pollen sensitization and TNF-αand IL-10 genotypes in the asthma induced by specific olive-pollen allergens.

scholarly journals Modulation of Androgen Receptor Transactivation by FoxH1

2005 ◽  
Vol 280 (43) ◽  
pp. 36355-36363 ◽  
Author(s):  
Guangchun Chen ◽  
Masatoshi Nomura ◽  
Hidetaka Morinaga ◽  
Eri Matsubara ◽  
Taijiro Okabe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Transforming Growth Factor ◽  
Microscopic Analysis ◽  
Transforming Growth Factor Β ◽  
Therapeutic Interventions ◽  
Protein Protein Interaction ◽  
Transactivation Potential ◽  
Series Of Experiments

Androgen signaling plays key roles in the development and progression of prostate cancer, and numerous ongoing studies focus on the regulation of androgen receptor (AR) transactivity to develop novel therapies for the treatment of androgen-independent prostate cancer. FoxH1, a member of the Forkhead-box (FOX) gene family of transcription factors, takes part in mediating transforming growth factor-β/activin signaling through its interaction with the Smad2·Smad4 complex. Using a series of experiments, we found that FoxH1 repressed both ligand-dependent and -independent transactivation of the AR on androgen-induced promoters. This action of FoxH1 was independent of its transactivation capacity and activin A but relieved by Smad2·Smad4. In addition, the repression of the AR by FoxH1 did not require deacetylase activity. A protein-protein interaction was identified between the AR and FoxH1 independently of dihydrotestosterone. Furthermore, a confocal microscopic analysis of LNCaP cells revealed that the interaction between the AR and FoxH1 occurred in the nucleus and that FoxH1 specifically blocked the foci formation of dihydrotestosterone-activated AR, which has been shown to be correlated with the AR transactivation potential. Taken together, our results indicate that FoxH1 functions as a new corepressor of the AR. Our observations not only strengthen the role of FoxH1 in AR-mediated transactivation but also suggest that therapeutic interventions based on AR-coregulator interactions could be designed to block both androgen-dependent and -independent growth of prostate cancer.

scholarly journals Comparison of TGF-β, IL-10 levels and LMP-1 in gastric and oropharyngeal carcinoma associated with EBV infection

2019 ◽  
Vol 32 (4) ◽  
pp. 236-239
Author(s):  
Anna Dworzanska ◽  
Malgorzata Strycharz-Dudziak ◽  
Ewa Kliszczewska ◽  
Bartlomiej Drop ◽  
Malgorzata Polz-Dacewicz
Keyword(s):  
Epstein Barr Virus ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Nuclear Antigen ◽  
Oropharyngeal Carcinoma ◽  
Barr Virus ◽  
Fresh Frozen ◽  
Epstein Barr

Abstract Increasing interest has been focused on the Epstein-Barr Virus (EBV)-associated cancers, including oropharyngeal cancer (OPC) and gastric cancer (GC). Different cytokines, growth factors and proteins take part in oncogenesis. The aim of our study was to generate a comparison of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) levels, as well as latent membrane protein (LMP-1), Epstein-Barr virus capsid antigen (EBVCA), Epstein-Barr virus nuclear antigen (EBNA) and early antigen (EA) frequency in the serum of patients with GC and OPC. The study involved 50 patients with diagnosed GC and 50 patients with OPC. All studied patients were EBV positive. Fresh-frozen tumor tissue fragments were tested using nested PCR assay for EBV DNA detection. Sera from all individuals were investigated using ELISA tests to detect the presence of EBVCA IgG, EBNA IgG, EA IgG, as well as to determine the levels of IL-10 and TGF-β. The obtained results were subjected to statistical analysis. In patients with GC, the levels of TGF-β and IL-10 were significantly higher than in OPC patients. However, the frequency and level of EBVCA, EBNA and EA in patients with OPC and GC were not significantly different. In contrast, TGF-β and IL-10 levels were significantly higher in EBVaGC, as compared to OPC, suggesting their role in gastric carcinogenesis. The differences in frequency of LMP-1 detection in patients with OPC and GC may suggest different mechanism of oncogenesis. Further studies are required to clarify the role of Epstein-Barr virus in cancer development.

scholarly journals Transforming Growth Factor β Production Is Inversely Correlated with Severity of Murine Malaria Infection

1998 ◽  
Vol 188 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Fakhereldin M. Omer ◽  
Eleanor M. Riley
Keyword(s):  
Growth Factor ◽  
Malaria Infection ◽  
Transforming Growth Factor ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Lethal Infection ◽  
Successful Control ◽  
Factor Α

We have examined the role of the immunomodulatory cytokine transforming growth factor (TGF)-β in the resolution and pathology of malaria in BALB/c mice. Circulating levels of TGF-β, and production of bioactive TGF-β by splenocytes, were found to be low in lethal infections with Plasmodium berghei. In contrast, resolving infections with P. chabaudi chabaudi or P. yoelii were accompanied by significant TGF-β production. A causal association between the failure to produce TGF-β and the severity of malaria infection was demonstrated by treatment of infected mice with neutralizing antibody to TGF-β, which exacerbated the virulence of P. berghei and transformed a resolving P. chabaudi chabaudi infection into a lethal infection, but had little effect on the course of P. yoelii infection. Parasitemia increased more rapidly in anti–TGF-β–treated mice but this did not seem to be the explanation for the increased pathology of infection as peak parasitemias were unchanged. Treatment of P. berghei–infected mice with recombinant TGF-β (rTGF-β) slowed the rate of parasite proliferation and prolonged their survival from 15 to up to 35 d. rTGF-β treatment was accompanied by a significant decrease in serum tumor necrosis factor α and an increase in interleukin 10. Finally, we present evidence that differences in TGF-β responses in different malaria infections are due to intrinsic differences between species of malaria parasites in their ability to induce production of TGF-β. Thus, TGF-β seems to induce protective immune responses, leading to slower parasite growth, early in infection, and, subsequently, appears to downregulate pathogenic responses late in infection. This duality of effect makes TGF-β a prime candidate for a major immunomodulatory cytokine associated with successful control of malaria infection.

scholarly journals The Potential Role of Regulatory B Cells in Idiopathic Membranous Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Zhaocheng Dong ◽  
Zhiyuan Liu ◽  
Haoran Dai ◽  
Wenbin Liu ◽  
Zhendong Feng ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Membranous Nephropathy ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Autoimmune Response ◽  
Idiopathic Membranous Nephropathy ◽  
Regulatory B Cells

Regulatory B cells (Breg) are widely regarded as immunomodulatory cells which play an immunosuppressive role. Breg inhibits pathological autoimmune response by secreting interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and adenosine and through other ways to prevent T cells and other immune cells from expanding. Recent studies have shown that different inflammatory environments induce different types of Breg cells, and these different Breg cells have different functions. For example, Br1 cells can secrete IgG4 to block autoantigens. Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the humoral immune response is dominant and the cellular immune response is impaired. However, only a handful of studies have been done on the role of Bregs in this regard. In this review, we provide a brief overview of the types and functions of Breg found in human body, as well as the abnormal pathological and immunological phenomena in IMN, and propose the hypothesis that Breg is activated in IMN patients and the proportion of Br1 can be increased. Our review aims at highlighting the correlation between Breg and IMN and proposes potential mechanisms, which can provide a new direction for the discovery of the pathogenesis of IMN, thus providing a new strategy for the prevention and early treatment of IMN.

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