Clinical Investigation of the Role of Interleukin-4 and Interleukin-13 in the Evolution of Prostate Cancer

Goldstein, Robert M.; Hanley, Charles; Morris, Jonathan C.; Cahill, Declan; Chandra, Ashish; Harper, Peter; Maher, John; Burbridge, S.

doi:10.3390/cancers3044281

Cited by 24 publications

(29 citation statements)

References 47 publications

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“…44 Analysis of benign and malignant prostate tissue demonstrates that the source of IL-4 is epithelial cells rather than infiltrating leukocytes. 45 It is generally recognized that TAMs may polarize to the M2 macrophage phenotype stimulated by IL-4, IL-10, and IL-13. 5 In our study, co-culture experiments were performed with cell co-culture inserts, which allowed no direct contact between PCa cells and macrophages, so that only soluble mediators were able to affect cellular activity.…”

Section: Discussionmentioning

confidence: 99%

PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment

Fan

Zhang

et al. 2017

Tumour Biol.

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Tumor-associated macrophages are key regulators of the complex interplay between tumor and tumor microenvironment. M2 Macrophages, one type of tumor-associated macrophages, are involved in prostate cancer growth and progression. Protein kinase C zeta has been shown to suppress prostate cancer cell growth, invasion, and metastasis as a tumor suppressor; however, its role in chemotaxis and activation of tumor-associated macrophages remains unclear. Here, we investigated the role of protein kinase C zeta of prostate cancer cells in regulation of macrophage chemotaxis and M2 phenotype activation. Immunohistochemistry was performed to analyze the expression of protein kinase C zeta and the number of CD206+ M2 macrophages in human prostate tissue. Macrophage chemotaxis and polarization were examined using Transwell migration assays and a co-culture system. Quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to detect M2 markers, protein kinase C zeta, interleukin-4, and interleukin-10 expression. We found the expression of protein kinase C zeta increased in prostate cancer tissues, especially in the early stage, and was negatively associated with tumor grade and the number of CD206+ macrophages. Inhibition of protein kinase C zeta expression in prostate cancer cells promoted chemotaxis of peripheral macrophages and acquisition of M2 phenotypic features. These results were further supported by the finding that silencing of endogenous protein kinase C zeta promoted the expression of prostate cancer cell-derived interleukin-4 and interleukin-10. These results suggest that protein kinase C zeta plays an important role in reducing infiltration of tumor-associated macrophages and activation of a pro-tumor M2 phenotype, which may constitute an important mechanism by which protein kinase C zeta represses cancer progression.

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Section: Discussionmentioning

confidence: 99%

PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment

Fan

Zhang

et al. 2017

Tumour Biol.

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“…Goldstein and coworkers, 2011, showed a different immunoreactivity of IL-4 in prostatic cells of BPH and prostatic cancer. Analysis of benign and malignant prostate tissues demonstrated that the source of IL-4 is the epithelial cells rather than infiltrating leukocyte [24]. In the normal group we observed a glandular epithelium with cellular monolayer and an IL-4 signal in the basal area, while in the WOT and placebo groups we observed hyperplasic and hypertrophic regions and a poor IL-4 expression in the luminal region (Figure 5(a)).…”

Section: Resultsmentioning

confidence: 95%

Anti-Inflammatory Effect of Dialyzable Leukocyte Extract in Autoimmune Prostatitis: Evaluation in Animal Model

Pérez-Alvarado

Gómez

Reyes

et al. 2017

BioMed Research International

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Objective. To evaluate the anti-inflammatory properties of Dialyzable Leukocyte Extract (DLE) in a murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods. Histopathological characterization, prostatein Enzyme-Linked Immunosorbent Assay, and immunohistochemical analysis for CD45, TNF-α, IFN-γ, IL-6, IL-17, and IL-4 molecules were done in prostatic Wistar rats treated with DLE, placebo, or Dexamethasone. Results. Histopathological analysis of animals induced to prostatitis showed inflammatory infiltrate, mainly constituted by leucocytes and mast cells as well as Benign Prostatic Hyperplasia. Serum prostatein concentrations were 14 times higher than those displayed by healthy animals. After DLE and Dexamethasone treatments, the inflammatory infiltrate decreased; the tissue morphology was similar to that of a normal prostate, and the prostatein decreased to the basal levels of healthy animals. DLE treatment produced a decreased expression of the cell surface marker CD45 and the proinflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17. On the other hand, the expression of anti-inflammatory cytokine IL-4 increased in both the Dexamethasone and DLE groups. Conclusion. DLE is able to modulate the inflammatory response in Experimental Autoimmune Prostatitis (EAP).

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“…Consistent with the present report, our previous study investigating the role of IL-17 in the context of CD4+ T-cell responses to TAAs documented a negative impact ofIL-17-producing T-cells in late-stage melanoma [ 20 ]. There are several other cytokines such as IL-4 and IL-13 that are known to have a negative impact on survival [ 31 , 32 ] and which would have been interesting to examine here, especially as we previously found that IL 4 was relevant in melanoma. IL-13 is known to regulate cancer invasion and metastasis in different cancers [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of circulating Her-2-reactive T-cells producing pro- and/or anti-inflammatory cytokines in elderly breast cancer patients

Bailur¹,

Derhovanessian²,

Gueckel³

et al. 2015

j. immunotherapy cancer

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BackgroundTreating elderly breast cancer patients remains a challenge but the increasing availability of immunotherapeutic approaches instills optimism that these tumours may also be susceptible to immune control. Because aging leads to a number of alterations in the immune system (“immunosenescence”) reflecting potential exhaustion which could compromise immunomodulatory antibody therapy, here we have assessed the immunocompetence of elderly breast cancer patients compared with a group of younger patients, and related this to the 5-year survival of the former.MethodsT-cell responses to Her-2 peptide pools in vitro were assessed by analyzing pro- and anti-inflammatory cytokine production by CD4+ and CD8+ T-cells in 40 elderly and 35 younger breast cancer patients.ResultsThe proportions of older and younger patients whose peripheral T-cells responded to Her-2 peptides in vitro were found to be similar, although a significantly higher fraction of younger patients possessed IL-2-producing CD4+ Her-2-reactive T-cells than in the elderly (p = 0.03). However, IL-2 production did not impart a survival benefit to the latter. In contrast, there was a survival benefit of possessing Her-2-reactive CD8+ T-cells, but this was abrogated in patients if they also had CD4+ Her-2-responsive T-cells that producedIL-5 and/or IL-17 (p = 0.01). This resulted in a 5-yr survival rate of only 29 % compared to 76 % for patients whose her-2-reactive CD4+ T-cells did not produceIL-5 and/or IL-17. Additionally, patients whose CD8+ T-cells produced TNF had a significantly better survival than those that did not (93 % compared to 52 %, p = 0.01), whereas no survival benefit was attributable to possessing IFN-γ-producing cells.ConclusionsElderly breast cancer patients appear perfectly immunocompetent to respond to Her-2 peptide pools in vitro, with response patterns very similar to younger patients. The nature of this response is associated with 5-year survival of these elderly patients, suggesting that boosting anti-tumor responses and modulating the nature of the T-cell response is likely to be effective even in potentially immunosenescent elderly breast cancer patients, and might be useful for predicting which patients are most likely to benefit from such treatments.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-015-0090-0) contains supplementary material, which is available to authorized users.

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Clinical Investigation of the Role of Interleukin-4 and Interleukin-13 in the Evolution of Prostate Cancer

Cited by 24 publications

References 47 publications

PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment

PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment

Anti-Inflammatory Effect of Dialyzable Leukocyte Extract in Autoimmune Prostatitis: Evaluation in Animal Model

Prognostic impact of circulating Her-2-reactive T-cells producing pro- and/or anti-inflammatory cytokines in elderly breast cancer patients

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