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Topics {✒️}

granulocyte–macrophage colony-stimulating factor granulocyte/macrophage colony-stimulating factor pre-existing t-cell responses dc-mediated t-cell stimulation il-1β/il-6/tnf-α/prostaglandin phosphate-buffered saline supplemented hla-dr-lin- cells higher véronique catros-quemener hla-dr-lin- cell percentage hla-dr-lin- dc phenotype hla-dr-lin- significantly increased article download pdf cross-prime exogenous antigens françoise bouet-toussaint propidium iodide inclusion/exclusion hla-dr-lin- phenotypes nk-sensitive cell lines full size image positive/propidium iodide negative hla-dr+lin- cells hla-dr-lin- cells positive/propidium iodide positive tumour necrosis factor-α hla-dr-lin- phenotype predominantly hla-dr+cd11c+ late-apoptotic leukemic blasts u-bottomed microtitre plates specialized antigen-presenting cells antigen-presenting cells blocks putrescine-treated dendritic cells mixed ductal-lobular carcinoma anatomo-pathological examinations tumor-induced immune-suppression peroxide-treated m74 cells leukemia-specific cytotoxic response 14% cd4+cd25+ctla4+ cells immature dendritic cell efs de rennes peroxide-treated tumour cells dendritic cell phenotype cell mediated immunity full access renal cell carcinoma hla-a2 class hla-dr+lin hla-dr-lin jean-jacques patard fitc-labelled opsonized bacteria monocyte-derived dcs dc-tuper stimulation procedure

Questions {❓}

• Lutz MB, Schuler G: Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?

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WebPage:
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         headline:Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency
         description:Dendritic cells (DCs) are antigen-presenting cells that are currently employed in cancer clinical trials. However, it is not clear whether their ability to induce tumour-specific immune responses when they are isolated from cancer patients is reduced relative to their ability in vivo. We determined the phenotype and functional activity of DCs from cancer patients and investigated the effect of putrescine, a polyamine molecule that is released in large amounts by cancer cells and has been implicated in metastatic invasion, on DCs. The IL-4/GM-CSF (granulocyte–macrophage colony-stimulating factor) procedure for culturing blood monocyte-derived DCs was applied to cells from healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used for DC pulsing. We investigated the effects of stimulation of autologous lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic activity of T cells was determined in the same target cells. Certain differences were observed between donors and breast cancer patients. The yield of DCs was dramatically weaker, and expression of MHC class II was lower and the percentage of HLA-DR-Lin- cells higher in patients. Whatever combination of maturating agents was used, expression of markers of mature DCs was significantly lower in patients. Also, DCs from patients exhibited reduced ability to stimulate cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was enhanced by up to 40% when DCs were from donors but only up to 10% when they were from patients. IFN-γ production was repeatedly found to be enhanced in donors but not in patients. By adding putrescine to DCs from donors, it was possible to enhance the HLA-DR-Lin- cell percentage and to reduce the final cytolytic activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. These putrescine-induced deficiencies were reversed by treating DCs with all-trans retinoic acid. These data are consistent with blockade of antigen-presenting cells at an early stage of differentiation in patients with breast cancer. Putrescine released in the microenvironmement of DCs could be involved in this blockade. Use of all-trans retinoic acid treatment to reverse this blockade and favour ex vivo expansion of antigen-specific T lymphocytes is of real interest.
         datePublished:2005-02-25T00:00:00Z
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            Healthy Donor
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            Cytolytic Activity
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            Cancer Research
            Oncology
            Surgical Oncology
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      headline:Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency
      description:Dendritic cells (DCs) are antigen-presenting cells that are currently employed in cancer clinical trials. However, it is not clear whether their ability to induce tumour-specific immune responses when they are isolated from cancer patients is reduced relative to their ability in vivo. We determined the phenotype and functional activity of DCs from cancer patients and investigated the effect of putrescine, a polyamine molecule that is released in large amounts by cancer cells and has been implicated in metastatic invasion, on DCs. The IL-4/GM-CSF (granulocyte–macrophage colony-stimulating factor) procedure for culturing blood monocyte-derived DCs was applied to cells from healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used for DC pulsing. We investigated the effects of stimulation of autologous lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic activity of T cells was determined in the same target cells. Certain differences were observed between donors and breast cancer patients. The yield of DCs was dramatically weaker, and expression of MHC class II was lower and the percentage of HLA-DR-Lin- cells higher in patients. Whatever combination of maturating agents was used, expression of markers of mature DCs was significantly lower in patients. Also, DCs from patients exhibited reduced ability to stimulate cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was enhanced by up to 40% when DCs were from donors but only up to 10% when they were from patients. IFN-γ production was repeatedly found to be enhanced in donors but not in patients. By adding putrescine to DCs from donors, it was possible to enhance the HLA-DR-Lin- cell percentage and to reduce the final cytolytic activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. These putrescine-induced deficiencies were reversed by treating DCs with all-trans retinoic acid. These data are consistent with blockade of antigen-presenting cells at an early stage of differentiation in patients with breast cancer. Putrescine released in the microenvironmement of DCs could be involved in this blockade. Use of all-trans retinoic acid treatment to reverse this blockade and favour ex vivo expansion of antigen-specific T lymphocytes is of real interest.
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      keywords:
         Renal Cell Carcinoma
         Healthy Donor
         Putrescine
         Cytolytic Activity
         Maturation Cocktail
         Cancer Research
         Oncology
         Surgical Oncology
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      affiliation:
            name:Centre AntiCancéreux de Rennes
            address:
               name:Service d'Oncologie Médicale, Centre AntiCancéreux de Rennes, Rennes, France
               type:PostalAddress
            type:Organization
      name:Laurent Sulpice
      affiliation:
            name:Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
            address:
               name:Departement de Chirurgie Viscérale, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
               type:PostalAddress
            type:Organization
      name:Jean-Jacques Patard
      affiliation:
            name:Faculté de Médecine de Rennes
            address:
               name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
               type:PostalAddress
            type:Organization
            name:Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
            address:
               name:Service d'Urologie, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
               type:PostalAddress
            type:Organization
      name:Noelle Genetet
      affiliation:
            name:Faculté de Médecine de Rennes
            address:
               name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
               type:PostalAddress
            type:Organization
            name:Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
            address:
               name:Laboratoire d'Immunologie, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
               type:PostalAddress
            type:Organization
      name:Véronique Catros-Quemener
      affiliation:
            name:Faculté de Médecine de Rennes
            address:
               name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
               type:PostalAddress
            type:Organization
            name:Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
            address:
               name:Laboratoire de Cytogénétique et Biologie Cellulaire, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
      name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
      name:Service de Gynécologie, Centre Hospitalier Universitaire de Rennes, Hôpital Sud, Rennes, France
      name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
      name:Laboratoire de Cytogénétique et Biologie Cellulaire, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
      name:Laboratoire d'Anatomo-Pathologie, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
      name:Service d'Oncologie Médicale, Centre AntiCancéreux de Rennes, Rennes, France
      name:Departement de Chirurgie Viscérale, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
      name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
      name:Service d'Urologie, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
      name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
      name:Laboratoire d'Immunologie, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France
      name:Groupe de Recherche en Thérapeutique AntiCancéreuse, UPRES 2261, Faculté de Médecine de Rennes, Rennes, France
      name:Laboratoire de Cytogénétique et Biologie Cellulaire, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Rennes, France

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