Interactions physiopathologiques du système immunitaire avec son micro-environnement

@article{russier_few-layer_2017,

title = {Few-Layer Graphene Kills Selectively Tumor Cells from Myelomonocytic Leukemia Patients},

author = {Julie Russier and Verónica León and Marco Orecchioni and Eri Hirata and Patrizia Virdis and Claudio Fozza and Francesco Sgarrella and Gianaurelio Cuniberti and Maurizio Prato and Ester Vázquez and Alberto Bianco and Lucia G Delogu},

doi = {10.1002/anie.201700078},

issn = {1521-3773},

year  = {2017},

date = {2017-01-01},

journal = {Angewandte Chemie (International Ed. in English)},

volume = {56},

number = {11},

pages = {3014--3019},

abstract = {In the cure of cancer, a major cause of today's mortality, chemotherapy is the most common treatment, though serious frequent challenges are encountered by current anticancer drugs. We discovered that few-layer graphene (FLG) dispersions have a specific killer action on monocytes, showing neither toxic nor activation effects on other immune cells. We confirmed the therapeutic application of graphene on an aggressive type of cancer that is myelomonocytic leukemia, where the monocytes are in their malignant form. We demonstrated that graphene has the unique ability to target and boost specifically the necrosis of monocytic cancer cells. Moreover, the comparison between FLG and a common chemotherapeutic drug, etoposide, confirmed the higher specificity and toxicity of FLG. Since current chemotherapy treatments of leukemia still cause serious problems, these findings open the way to new and safer therapeutic approaches.},

keywords = {Acute, cancer therapy, Chronic, Cultured, graphene, Graphite, Humans, I2CT, Immune System, leukemia, Leukocytes, Mononuclear, Myeloid, Myelomonocytic, myelomonocytic leukemia, Nanomaterials, Particle Size, Surface Properties, Team-Bianco, Tumor Cells},

pubstate = {published},

tppubtype = {article}

}

@article{mairhofer_impaired_2015,

title = {Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model},

author = {David G Mairhofer and Daniela Ortner and Christoph H Tripp and Sandra Schaffenrath and Viktor Fleming and Lukas Heger and Kerstin Komenda and Daniela Reider and Diana Dudziak and Suzie Chen and Jürgen C Becker and Vincent Flacher and Patrizia Stoitzner},

doi = {10.1038/jid.2015.241},

issn = {1523-1747},

year  = {2015},

date = {2015-11-01},

journal = {The Journal of Investigative Dermatology},

volume = {135},

number = {11},

pages = {2785--2793},

abstract = {Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies.},

keywords = {Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity},

pubstate = {published},

tppubtype = {article}

}

@article{ali-boucetta_multiwalled_2008,

title = {Multiwalled carbon nanotube-doxorubicin supramolecular complexes for cancer therapeutics},

author = {Hanene Ali-Boucetta and Khuloud T Al-Jamal and David McCarthy and Maurizio Prato and Alberto Bianco and Kostas Kostarelos},

doi = {10.1039/b712350g},

issn = {1359-7345},

year  = {2008},

date = {2008-01-01},

journal = {Chemical Communications (Cambridge, England)},

number = {4},

pages = {459--461},

abstract = {Multiwalled carbon nanotube aqueous dispersions using block copolymers are able to form supramolecular complexes with the aromatic chromophore and anticancer agent doxorubicin via pi-pi stacking and enhance its cytotoxic activity.},

keywords = {Antineoplastic Agents, Breast Neoplasms, carbon, Cultured, Doxorubicin, Electron, Humans, I2CT, Microscopy, Nanotubes, Team-Bianco, Transmission, Tumor Cells},

pubstate = {published},

tppubtype = {article}

}

@article{van_mierlo_activation_2004,

title = {Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication},

author = {Geertje J D van Mierlo and Zita F H M Boonman and Hélène M H Dumortier and Annemieke Th den Boer and Marieke F Fransen and Jan Nouta and Ellen I H van der Voort and Rienk Offringa and René E M Toes and Cornelis J M Melief},

doi = {10.4049/jimmunol.173.11.6753},

issn = {0022-1767},

year  = {2004},

date = {2004-12-01},

journal = {Journal of Immunology (Baltimore, Md.: 1950)},

volume = {173},

number = {11},

pages = {6753--6759},

abstract = {The fate of naive CD8(+) T cells is determined by the environment in which they encounter MHC class I presented peptide Ags. The manner in which tumor Ags are presented is a longstanding matter of debate. Ag presentation might be mediated by tumor cells in tumor draining lymph nodes or via cross-presentation by professional APC. Either pathway is insufficient to elicit protective antitumor immunity. We now demonstrate using a syngeneic mouse tumor model, expressing an Ag derived from the early region 1A of human adenovirus type 5, that the inadequate nature of the antitumor CTL response is not due to direct Ag presentation by the tumor cells, but results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC. Although this event results in division of naive CTL in tumor draining lymph nodes, it does not establish a productive immune response. Treatment of tumor-bearing mice with dendritic cell-stimulating agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector function capable to eradicate established tumors. For efficacy of anti-CD40 treatment, CD40 ligation of host APC is required because adoptive transfer of CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor-bearing mice did not lead to productive antitumor immunity after CD40 triggering in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb with respect to CD8(+) CTL efflux and tumor eradication. Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity.},

keywords = {Adenovirus E1A Proteins, Animals, Antibodies, Antigen-Presenting Cells, Antigens, CD11c Antigen, CD40 Antigens, Cross-Priming, Cultured, Cytotoxic, Cytotoxicity, Dendritic Cells, Dumortier, Epitopes, Experimental, I2CT, Immunologic, Inbred C57BL, Injections, Intralesional, Intravenous, Knockout, Male, Mice, Monoclonal, Neoplasms, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic, tumor, Tumor Cells, Viral},

pubstate = {published},

tppubtype = {article}

}