Les Cellules Dendritiques en Immunothérapie anti

Université de Nantes
Faculté de Médecine et Techniques Médicales
Les Cellules Dendritiques en Immunothérapie
anti-tumorale : caractérisation et maturation
THESE DE DOCTORAT
Ecole Doctorale CHIMIE BIOLOGIE
Discipline : Sciences de la vie et de la Santé
Spécialité : Immunologie
Présentée et soutenue publiquement par
Séverine TANGUY-ROYER
Le 2 octobre 2008, devant le jury ci-dessous
Rapporteurs : Clotilde THERY, Chargée de recherche, Paris
Florence VELGE ROUSSEL, Maître de conférences,
Tours
Examinateur : Pascale JEANNIN, PU-PH, Angers
Directeur de Thèse : Marc GREGOIRE, Directeur de recherche, Nantes

Les cellules dendritiques en immunothérapie anti-tumorale : caractérisation et maturation
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ABREVIATIONS
aGvHD: « acute graft versus host desease »
ACT: “adoptive cell transfert”
ADCC: « antibody-dependent cell-mediated cytotoxicity”
ADN: acide désoxyribonucléique
ADNc: ADN complémentaire d’un brin d’ARN
AEP: “asparagine-specific endopeptidase”
AICD: “activation-induced cell death”
APRIL: “a proliferation-inducing ligand”
ARN: acide ribonucléique
ATP : adénosine triphosphate
B2R : récepteur à la bradykinine
B7-H: “B7-homologue”
BAFF / BlyS: “B cell-activating factor / B lymphocyte stimulator”
BCR: “B-cell receptor”
BDCA: “blood DC antigen”
BTLA: “B- and T-lymphocyte attenuator”
CD: “cluster of differentiation”
CLEC: “C-type lectin-like receptor”
CLIP: “class II-associated Ii-derived peptide”
CLR: “c-type lectin receptor”
CMH : complexe majeur d’histocompatibilité
CMV: cytomégalovius
CO : monoxyde de carbone
COX :cyclooxygénase
APC : « antigen presenting cell » (ou CPA)
CR: “complement recepteur”
CRD: “carbohydrate recognition domain”
CSF-R: “colony stimulating factor receptor”
CTL: “cytotoxic T lymphocyte”
CTLA-4: “cytotoxic T lymphocyte-associated 4”
DAK: “DC-mediated activation of killer cells”
DC: “dendritic cell”
DCAR: “DC immunoactivating receptor”
DCIR: “dendritic cell immunoreceptor”
DC-SIGN: “dendritic cell-specific ICAM-3-grabbing nonintegrin”
Dectin: “DC-associated C-type lectin”
dsRNA: “double strand RNA”
EAT2: “EWS/FLI1-activated transcript 2”
EBI3: “Epstein Barr virus-induced gene 3”
FcR: récepteur au fragment Fc des Ig
FGF: “fibroblast growth factor”
GITR: “glucocorticoid-induced TNFR-related gene”
GM-CSF: “granulocyte macrophage – colony stimulating factor”
GP96: glycoprotéine 96
GrB2: “growth factor receptor-bound protein 2”

Les cellules dendritiques en immunothérapie anti-tumorale : caractérisation et maturation
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GTP: guanine tri-phosphate
HEV: “high endothelial veinule”
HIV: “human immunodeficiency virus”
HLA: “human leukocyte antigen”
HMGB1: “high mobility group box 1”
HO-1: “heme oxygenase-1”
HSP: “heat-shock protein”
HVEM: “Herpesvirus entry mediator”
ICAM: “intercellular adhesion molecule”
ICOS: “inducible T-cell costimulator”
IDO: “indoleamine dioxygenase”
IFN: interféron
IFNAR : “IFNalpha recepteur”
Ig : Immunoglobuline
IL: interleukine
IL3Ra: chaîne alpha du récepteur { l’interleukine 3
IL1RA: “IL1 recepteur antagonist”
i-NOS: “ inducible- nitric oxyde synthase”
IP-10: “interferon-inducible protein 10”
ITAM: “immunoreceptor tyrosine-based activation motif”
ITIM: “immunoreceptor tyrosine-based inhibitory motif”
KIR: “killer-cell immunoglobulin-like receptor”
IRF: “interferon regulatory factor”
LAK: “lymphokine activated killer cell”
LAT: “linker for activation of T cells”
LB: lymphocyte B
LC: cellule de Langerhans
LCA: “leukocyte common antigen”
LFA: “lymphocyte function-associated antigen”
LMP: “large multicatalytic protease”
LOX-1: “lectin-like oxidized low-density lipoprotein receptor -1
LPS: lipopolysaccharide
LT: lymphocyte T
MIIC: “MHC II compartment”
MCM: “monocyte conditionned medium”
MCP: “monocyte chemotactic protein”
M-CSF: “macrophage-colony stimulating factor”
MDA-5: “melanoma differentiation-associated gene 5” (=Helicard)
MDC: “macrophage-derived chemokine”
MICL: “myeloid inhibitory C-type lectin-like receptor”
Mig : “monokine induced by gamma interferon”
MIP : “macrophage inflammatory protein”
MMP: “matrix metalloproteinase”
MPS: système phagocytaire mononucléaire
MR: “mannose receptor” (MMR: macrophage mannose receptor)
1-MT: 1-méthyl tryptophane
MUC: mucine
MyD88: “myeloid differentiation primary response gene 88”
NALP: “NACHT-LRR-PYR-containing proteins”

Les cellules dendritiques en immunothérapie anti-tumorale : caractérisation et maturation
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NFkB: “nuclear factor kappa-B”
NK: “natural killer”
NKR: “natural killer recepteur”
NKT cell: “natural killer T cell”
NLR: “Nod-like receptor”
NO: “nitric oxide”
Nod: “nucleotide-binding oligomerisation domain”
PAF: “platelet-activating factor”
PAMP: “pathogen-associated molecular pattern”
PD-1: “programmed death-1”
PD-L: “programmed death – ligand”
PKR: “double-stranded RNA-dependent protein kinase”
polyIC: “polyinositic cytidilic acid”
PRR: “pattern recognition receptor”
RANK: “receptor activator of NF-kappa-B”
RANTES: “regulated upon activation, normally T-expressed and presumably secreted”
RBP-Jk: “recombination signal-binding protein 1 for J-kappa”
RE: réticulum endoplasmique
RIG-1: “retinoic acid-inducible gene 1”
RLR: “RIG-1-like receptor”
SAP: “SLAM-associated protein”
SARM: “sterile alpha motif and armadillo motif domain-containing protein”
SDF-1: “stromal cell-derived factor 1”
SHP2: phosphatase à domaine SH2
SLAM: “signalling lymphocyte activation molecule”
SLC: “secondary lymphoid tissue chemokine”
SMAC: “supramolecular activation cluster”
SP-A: “surfactant protein-A”
SR: “scavenger receptor”
STAT: “signal transducer and activator of transcription”
TAP: “transporter associated with antigen processing”
TARC: “thymus and activation-regulated chemokine”
TEM: lymphocytes T effecteurs-mémoires
TCM: lymphocytes T centraux-mémoires
TCR: “T-cell receptor”
TGF: “tissue growth factor”
Th1: lymphocyte T helper de type 1
Th2: lymphocyte T helper de type 2
TERT: “telomerase reverse transcriptase”
TIL: “tumor-infiltrating lymphocyte”
TIMP: “tissue inhibitor of metalloproteinase”
TIR: “TLR / IL1R domain”
TIRAP: “TIR-domain-containing adaptor protein (= MAL)”
TLR: “toll-like receptor”
TNF: “tumor necrosis factor”
TNFR: “TNF receptor”
TRAIL: “TNF-related apoptosis-inducing ligand”
TRAM: “TRIF-related adaptor molecule (= TIRP ou TICAM-2)”
TRANCE: “TNF-related activation-induced cytokine”

Les cellules dendritiques en immunothérapie anti-tumorale : caractérisation et maturation
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Treg: lymphocyte T régulateur
Ts: lymphocyte T suppresseur
TRIF: “TIR-domain-containing adaptor inducing IFN-β (= TICAM-1)”
UTP: Uridine triphosphate
VIP: “vasoactive intestinal peptide”
VLA: “very late activation protein”
WARS: “tryptophanyl t-RNA synthetase”