Distribution of langerhans cells and HLA class II molecules in prostatic carcinomas of different histopathological grade

Bigotti, Giulio; Coli, Antonella; Castagnola, Diana

doi:10.1002/pros.2990190108

Cited by 52 publications

(19 citation statements)

References 28 publications

(11 reference statements)

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“…8 As it has been shown, DC numbers decrease in prostate cancer tissues in comparison to benign prostatic hyperplasia (BPH) tissues 24 and the levels of infiltrating DC further decreases with the increase of anaplastic grade. 25 Our previous experiments demonstrated that prostate cancer cells induced apoptosis of human DC during the in vitro co-incubation. 4 Since DC play a crucial role in the mounting of host antitumor immune responses, 5,26 it is conceivable that their elimination might effectively suppress the immune system.…”

Section: Discussionmentioning

confidence: 98%

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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Section: Discussionmentioning

confidence: 98%

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

Pirtskhalaishvili

Shurin

Esche

et al. 2001

Prostate Cancer Prostatic Dis

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“…S-100 is a small acidic regulatory protein involved in a wide range of cellular processes and exhibits relative tissue specificity for DCs and cells of neural origin, including melanoma cells (Heizmann et al, 2002). The density of DCs, using either CD1a or S-100 as markers for DC, has been reported for a variety of human cancers including cervix (Younes et al, 1968;Bethwaite et al, 1996), ovary (Eisenthal et al, 2001), lung (Bassett et al, 1974;Fox et al, 1989;Zeid and Muller, 1993), larynx (Schenk, 1980), salivary glands (David and Buchner, 1980), skin (Gatter et al, 1980), breast (Hillenbrand et al, 1999;Coventry et al, 2002), thymus (Hammar et al, 1986), oesophagus (Matsuda et al, 1990), stomach (Tsujitani et al, 1987), pancreas (Dallal et al, 2002), thyroid (Schroder et al, 1988;Willgeroth et al, 1992), colon (Ambe et al, 1989), nasopharynx (Nomori et al, 1986;Gallo et al, 1991a;laryngeal (Gallo et al, 1991b)), oral (Kikuchi et al, 2002), prostate, bladder and kidney (Bigotti et al, 1991;Inoue et al, 1993;Troy et al, 1998aTroy et al, , b, 1999. Furthermore, DC numbers, as measured using either CD1a or S-100 antibodies, have been positively associated with improved outcome (increased survival) for many of these cancers, although the mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer

Coventry

Morton

2003

Br J Cancer

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Infiltrating CD1aþ dendritic cells (DCs) have been associated with increased survival in a number of human cancers. This study investigated DC infiltration within breast cancers and the association with survival. Classical established prognostic factors, of tumour size, lymph node status, histological grade, lympho-vascular invasion, the KI-67 (MIB-1) fraction and the Nottingham Prognostic Index (NPI) were also compared. A total of 48 breast cancer patients were followed from the time of surgery and CD1a density analysis for 5 years or until death. Our data set validated previous studies, which show a relationship between survival and the NPI (Po0.001), tumour size (Po0.01) and lymph node status (Po0.05). Although more patients were alive at the 5-year time point in the group with higher CD1a DC density than the lower CD1a DC group, this failed to reach statistical significance at the P ¼ 0.05 level. Analysis at 10 years postsurgery is required to investigate the association further.

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“…Prostate cancer was found to be sparse in tumour-infiltrating DC in comparison with benign prostate hyperplasia and normal prostate tissues. 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).…”

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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Distribution of langerhans cells and HLA class II molecules in prostatic carcinomas of different histopathological grade

Cited by 52 publications

References 28 publications

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

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

CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer

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

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