Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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

La toxicologie nucléaire

International audienceLa toxicologie nucléaire humaine vise à étudier, dans le cas d'une incorporation dans l'organisme, le comportement et les effets biologiques néfastes des radionucléides (RN) et/ou d'éléments chimiques issus du fonctionnement normal ou d'une situation accidentelle des installations du cycle électronucléair

La toxicologie nucléaire

International audienceLa toxicologie nucléaire humaine vise à étudier, dans le cas d'une incorporation dans l'organisme, le comportement et les effets biologiques néfastes des radionucléides (RN) et/ou d'éléments chimiques issus du fonctionnement normal ou d'une situation accidentelle des installations du cycle électronucléair

Treatment of radiological contamination: a review

International audienceAfter nuclear accidents, people can be contaminated internally via ingestion, inhalation and via intact skin or wounds. The assessment of absorbed, committed doses after internal exposure is based on activity measurement by in vivo or in vitro bioassay. Estimation of dose following internal contamination is dependent on understanding the nature and form of the radionuclide. Direct counting methods that directly measure γ -rays coming from within the body or bioassay methods that measure the amount of radioactive materials in urine or feces are used to estimate the intake, which is required for calculating internal exposure doses. The interpretation of these data in terms of intake and the lifetime committed dose requires knowledge or making assumptions about a number of parameters (time, type of exposure, route of the exposure, physical, biological and chemical characteristics) and their biokinetics inside the body. Radioactive materials incorporated into the body emit radiation within the body. Accumulation in some specific organs may occur depending on the types of radioactive materials. Decorporation therapy is that acceleration of the natural rate of elimination of the contaminant will reduce the amount of radioactivity retained in the body. This article presents an overview of treatment of radiological contamination after internal contamination

Selecting a Toxicity Reference Value (TRV) for lindane to assess health risk associated with a school contamination in France.

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Mercury, elemental: Recommended form to be used for the proposed classification and labelling, DG XI of a dangerous substance under Directive 67/548/EEC

Prepared by the Working group "Mercury Classification", AFSSET (France) and Toxicology Unit, INRS (France)Etat-Membre rapporteur: France /Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, AFSSET, FOR THE COMMISSION OF THE CLASSIFICATION AND LABELLING OF DANGEROUS SUBSTANCES, European Communitiesinfo:eu-repo/semantics/publishe

Mercuric Chloride, elemental: Recommended form to be used for the proposed classification and labelling, DG XI of a dangerous substance under Directive 67/548/EEC

Prepared by the Working group "Mercury Classification", AFSSET (France) and Toxicology Unit, INRS (France)Etat-Membre rapporteur: France /Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, AFSSET, FOR THE COMMISSION OF THE CLASSIFICATION AND LABELLING OF DANGEROUS SUBSTANCES, European Communitiesinfo:eu-repo/semantics/publishe