MHC class I and II expression in prostate carcinoma and modulation by interferon-alpha and -gamma

Bander, Neil H.; Yao, Daniel; Li, He; Chen, Yao‐Tseng; Steiner, Melissa G.; Zuccaro, Wendy; Moy, P.

doi:10.1002/(sici)1097-0045(19971201)33:4<233::aid-pros2>3.0.co;2-i

Cited by 90 publications

(78 citation statements)

References 16 publications

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“…The number of DC further decreased in the high-grade prostate carcinomas (Bigotti et al, 1991;Davidson et al, 1997;Troy et al, 1998), which carry the worst prognosis (Eastham and Scardino, 1998). It is possible that active suppression of the host immune system, together with loss or attenuation of class I expression by prostate cancer (Bander et al, 1997) may be responsible for the depressed immunity in prostate cancer patients (Ivshina et al, 1995;Healy et al, 1998;Salgaller et al, 1998). Understanding of prostate cancer immunobiology and, in particular, the immunobiology of DC, will help in the development of effective immunotherapy for this disease.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins

et al. 2000

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Summary Prostate cancer is the most common cancer in men in the United States, and second in cancer-induced mortality. It is likely that tumour-induced immunosuppression is one of the reasons for low treatment efficacy in patients with advanced prostate cancer. It has been recently demonstrated that prostate cancer tissue is almost devoid of dendritic cells (DC), the major antigen-presenting cells responsible for the induction of specific antitumour immune responses. In this study, we have tested the hypothesis that prostate cancer induces progressive suppression of the DC system. We found that co-incubation of human DC with three prostate cancer cell lines led to the high levels of premature apoptosis of DC, which were significantly higher than in DC cultures co-incubated with normal prostate cells or blood leucocytes. Stimulation of DC for 24 hours with CD40 ligand (CD154), IL-12 or IL-15 prior to their co-incubation with prostate cancer cells resulted in a significant increase in DC survival in the tumour microenvironment. Furthermore, activation of DC with these cytokines was also accompanied by increased expression of the anti-apoptotic protein Bcl-x L in DC, suggesting a possible mechanism involved in DC protection from apoptotic death. In summary, our data demonstrate that prostate cancer induces active elimination of DC in the tumour microenvironment. Stimulation of DC by CD154, IL-12 or IL-15 leads to an increased expression of the anti-apoptotic protein Bcl-x L and increased resistance of DC to prostate cancer-induced apoptosis. These results suggest a new mechanism of tumour escape from immune recognition and demonstrate the cytokinebased approaches which might significantly increase the efficacy of DC-based therapies for cancer. (2000) 83(4), 506-513 © 2000 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1289, available online at http://www.idealibrary.com on immunologic response of the host and allowing tumour to progress (Shurin, 1999).When it was generally accepted that DC play a major role in the induction and development of specific immunologic responses, several clinical trials were initiated which used DC-based immunotherapies to treat cancer patients, including patients with prostatic carcinomas. For instance, Salgaller et al (1998) treated prostate cancer patients using DC pulsed with prostate membrane specific antigen (PMSA)-associated peptides. The results of this and similar clinical trials were quite optimistic. However, presence of patients with limited or no responses suggests that immunobiology of DC in in vivo tumour microenvironment might be different from our expectations and indicates the actual need for the improvement of modern DC-based immunotherapies. We hypothesized that one of the reasons for the limited efficacy of the immune responses in treated patients may be the prostate cancerinduced suppression and elimination of DC.Premature apoptosis of DC, induced by different tumour cell lines, has been described early (Esche et al, 1999). However, signal transduction pathways...

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Section: Discussionmentioning

confidence: 99%

Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins

et al. 2000

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“…In fact, prostate cancer cells have often been shown to be weakly immunogenic due to the lack of major histocompatibility complex (MHC) molecules on their surface. 1 Furthermore, tumor-induced immunosuppression was also repeatedly documented in prostate cancer patients. 2,3 We have recently demonstrated that human prostate cancer cell lines caused apoptosis of dendritic cells (DC), the key regulatory cells of the immune system responsible for the induction of specific antitumor immune responses.…”

Section: Introductionmentioning

confidence: 97%

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Pirtskhalaishvili

Shurin

Esche

et al. 2001

Prostate Cancer Prostatic Dis

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We have recently shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DC), which are responsible for the induction of specific antitumor immune responses. Here we have evaluated the effect of murine PCa cells RM-1 on the survival of immature and tumor necrosis factor-a (TNF-a)-stimulated mature DC. PCa cells and DC were co-incubated for 24 -48 h and DC apoptosis was assessed by morphologic criteria, Annexin V assay, and TUNEL staining. We have shown that co-incubation of RM-1 cells with DC is accompanied by an increased level of DC apoptosis, which was mediated by decreased expression of anti-apoptotic protein Bcl-2. Stimulation of DC maturation by TNF-a resulted in increased resistance of DC to PCa-induced apoptosis. In TNF-a treated mature DC, but not in immature DC, the expression of Bcl-2 was not blocked after exposure to RM-1-derived factors. Thus, these data suggest that TNF-a-induced maturation of DC increases their resistance to PCa induced apoptosis. This is likely to be due to the stabilizing of the expression of anti-apoptotic protein Bcl-2. The difference in the sensitivity of mature and immature DC to PCa-induced cell death should be considered during the design of DC-based clinical trials for PCa patients. Prostate Cancer and Prostatic Diseases (2001) 4, 221-227.

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“…Several types of immune cells, such as cytotoxic T lymphocytes (CTL) and natural killer (NK) cells have demonstrated anti-cancer activity and may represent a promising cell therapy for the treatment of prostate cancer. However, prostate cancer is able to evade CTL immune surveillance through frequent loss of MHC class I and II expression in cancer cells and tissues (29)(30)(31)(32)(33), indicating that attempts to activate T cells may not be a successful strategy for the treatment of prostate cancer. On the other hand, many attempts were made to enhance activity of NK cells and expand their population, which are suppressed in prostate cancer patients (34,35).…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of the human LNCaP prostate cancer cells to the apoptotic effect of marina crystal minerals (MCM) in vitro

Ghoneum¹

2009

Oncol Rep

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Abstract. Prostate cancer is one of the most frequent cancers among men in the United States. In the current study, we examined the susceptibility of the human LNCaP prostate cancer cells to the apoptotic effect of marina crystal minerals (MCM), a crystallized mixture of minerals and trace elements from sea water, in vitro. Cancer cells were cultured with MCM at different concentrations (0-1000 μg/ml). At day 3, MCM exhibited a marked apoptotic effect on LNCaP cells as measured by propidium iodide (PI) and Giemsastained cytospin preparations. The apoptotic effect was dosedependent: a 2-fold increase in the level of apoptosis over the control cells was observed at low concentrations of 50 μg/ml, maximial (3-fold) at a concentration of 500-1000 μg/ml. The mechanism by which MCM induces apoptosis was examined. Flow cytometery analysis demonstrated that mitochondrial membrane potential was significantly decreased post-treatment with MCM at low concentrations of 100 μg/ml. In addition, Western blot analysis showed that the level of anti-apoptotic molecule Bcl-2 in LNCaP cells decreased upon treatment with MCM. We conclude that MCM has an apoptotic effect toward human prostate cancer cells, which may suggest its broader potential as an innovative, non-toxic anti-cancer agent. IntroductionProstate cancer is the most common non-cutaneous cancer among males. Prostate-specific antigen (PSA) and digital rectal examination (DRE) are the 2 components necessary for a modern screening program. While prostate cancer can be a slow-growing cancer, thousands of men die of the disease each year. According to recent figures from the American Cancer Society, 220,900 new cases were diagnosed in 2003 and 28,900 men were predicted to die of prostate cancer. Prostate cancer is rarely diagnosed in men younger than 40 years and it is uncommon in men younger than 50 years. Prostate cancer is also found during autopsies performed following other causes of death. The rate of this latent-or autopsydiagnosed cancer is much greater than that of clinical cancer. In fact, it may be as high as 80% by age 80 years. In addition, genetic studies suggest that a strong familial predisposition may be responsible for as many as 5-10% of prostate cancer cases (1,2). Most prostate cancers are adenocarcinomas (95%). Prior to metastasis, oncologists mainly rely on surgery, chemotherapy and radiation therapy for cancer treatment of prostate cancers. The destruction of cells by chemotherapy and radiation therapy is indiscriminate with serious side effects. In addition to being toxic, both chemotherapy and radiation therapy are also immune-suppressive, mutagenic and carcinogenic (3-6). Hormone therapy is also commonly used to treat prostate cancer. Most clinical trials to date have evaluated flutamide or nilutamide for the treatment of advanced prostate cancer. Results showed that these drugs resulted in a survival increase of only 8% at 5 years (7).In the field of prostate cancer therapeutics, it is known that some cancers respond well to specific chemotherapy ...

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MHC class I and II expression in prostate carcinoma and modulation by interferon-alpha and -gamma

Cited by 90 publications

References 16 publications

Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins

Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Susceptibility of the human LNCaP prostate cancer cells to the apoptotic effect of marina crystal minerals (MCM) in vitro

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