Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes

BACKGROUND: Early clinical trials, mostly in the setting of melanoma, have shown that dendritic cells (DCs) expressing tumor antigens induce some immune responses and some clinical responses. A major difficulty is the extension to other tumors, such as breast carcinoma, for which few defined tumor-associated antigens are available. We have demonstrated, using both prostate carcinoma and melanoma as model systems, that DCs loaded with killed allogeneic tumor cell lines can induce CD8(+ )T cells to differentiate into cytotoxic T lymphocytes (CTLs) specific for shared tumor antigens. METHODS: The present study was designed to determine whether DCs would capture killed breast cancer cells and present their antigens to autologous CD4(+ )and CD8(+ )T cells. RESULTS: We show that killed breast cancer cells are captured by immature DCs that, after induced maturation, can efficiently present MHC class I and class II peptides to CD8(+ )and CD4(+ )T lymphocytes. The elicited CTLs are able to kill the target cells without a need for pretreatment with interferon gamma. CTLs can be obtained by culturing the DCs loaded with killed breast cancer cells with unseparated peripheral blood lymphocytes, indicating that the DCs can overcome any potential inhibitory effects of breast cancer cells. CONCLUSION: Loading DCs with killed breast cancer cells may be considered a novel approach to breast cancer immunotherapy and to identification of shared breast cancer antigens

Cross-Priming of Naive Cd8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells

The goal of tumor immunotherapy is to elicit immune responses against autologous tumors. It would be highly desirable that such responses include multiple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-priming. That is, one could load the DC with tumor lines of any human histocompatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA+CD27+CD8+ T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201+ naive T cells primed by DCs loaded with HLA-A201− melanoma cells are able to kill several HLA-A201+ melanoma targets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obtained with cells from metastatic melanoma patients. This demonstration of cross-priming against shared tumor antigens builds the basis for using allogeneic tumor cell lines to deliver tumor antigens to DCs for vaccination protocols

The efficacy of therapeutic plasma exchange in COVID-19 patients on endothelial tightness in vitro is hindered by platelet activation

Coronavirus disease (COVID)-19 is characterised in particular by vascular inflammation with platelet activation and endothelial dysfunction. During the pandemic, therapeutic plasma exchange (TPE) was used to reduce the cytokine storm in the circulation and delay or prevent ICU admissions. This procedure consists in replacing the inflammatory plasma by fresh frozen plasma from healthy donors and is often used to remove pathogenic molecules from plasma (autoantibodies, immune complexes, toxins, etc.). This study uses an in vitro model of platelet-endothelial cell interactions to assess changes in these interactions by plasma from COVID-19 patients and to determine the extent to which TPE reduces such changes. We noted that exposure of an endothelial monolayer to plasmas from COVID-19 patients post-TPE induced less endothelial permeability compared to COVID-19 control plasmas. Yet, when endothelial cells were co-cultured with healthy platelets and exposed to the plasma, the beneficial effect of TPE on endothelial permeability was somewhat reduced. This was linked to platelet and endothelial phenotypical activation but not with inflammatory molecule secretion. Our work shows that, in parallel to the beneficial removal of inflammatory factors from the circulation, TPE triggers cellular activation which may partly explain the reduction in efficacy in terms of endothelial dysfunction. These findings provide new insights for improving the efficacy of TPE using supporting treatments targeting platelet activation, for instance

Les impacts constitutionnels et politiques du renvoi relatif a la secession du Quebec /

Un autre essai sur la sempiternelle question de l'unite canadienne, deplorez-vous presentement. Pis encore, ajoutez-vous, on y aborde une fois de plus l'ennuyeuse et l'ennuyante problematique constitutionnelle. Et pourquoi l'auteur a-t-il choisi un tel sujet? Parce qu'il fait partie de la race des fatigants mais infatigables maniaques de cet incessant debat qu'est celui des Deux Solitudes? Possible. Surement meme. Mais il y a plus: le Renvoi relatif a la secession du Quebec ne represente pas qu'un simple episode de la saga constitutionnelle canadienne. Vraisemblablement, ces implications pratiques pourraient un jour sceller l'issue du debat. Certes, le mouvement separatiste quebecois, loin d'etre moribond, ne s'eteindra pas sur la seule base d'une decision de la Cour supreme du Canada. Pretendre le contraire releve de la fantaisie, de l'outrecuidance ou encore, d'un manque tangible de pragmatisme politique. Toutefois, un fait persiste: applique in extenso, l'Avis s'avere une serieuse embuche sur le chemin menant a l'independance. (Abstract shortened by UMI.

Wells' syndrome-like reaction following Argas reflexus bites

International audienc

Soil microbial respiration and PICT responses to an industrial and historic lead pollution: a field study

International audienceno abstrac