Cellules myeloides suppressives M1 – UE9 29 Octobre 2015 Mikael ROUSSEL...
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Transcript of Cellules myeloides suppressives M1 – UE9 29 Octobre 2015 Mikael ROUSSEL...
Hematopoiese
Gabrilovich, Nat Rev Immunol, 2012
LymphNode
Bone Marrow
BloodBlood
Tissues
FL
MPP : progéniteur multipotent
CMLP : progéniteur myélo-lympho commun
CLP : progéniteur lymphoïde commun
CMP : progéniteur myéloïde commun
CDP : progéniteur DC commun
GMP : progéniteur granuleux et macrophages
MCP progéniteur mastocytes
MDP : progéniteur macrophage et DC
MEP : progéniteur megacaryocyte et érythroïde
Microenvironment and cancer
Wolf-Herman, Nat Rev Cancer, 2012De Visser, Nat Rev Cancer, 2006
FL
Microenvironment and cancer
Narendra, Inflamm Res, 2013
FL
Populations myéloides suppressives
• Suppressive = régulatrice = immunomodulatrice• Supprime la réponse T et NK
Large family of tolerogenic cells:• Treg,• Breg,• tolerogenic DC,• MSC,• regulatory macrophages,• MDSC
• turn-on / turn-off• Complex regulation• Impair T effector and NK functions
• IL-10, TGF-b• aa depletion (IDO, Arginase)
Gabrilovich, Nat Rev Immunol, 2012
Changes that occur in myeloid cells in cancer
DC :-APC-activate T-link between innate and adaptative
Monocyte-in blood-APC ((<DC)-Phagocytosis-Cytokine production-migrate to the tissue
Macrophage-in tissue-APC-Phagocytosis-Inflammation/anti-inflammation
Gabrilovich, Nat Rev Immunol, 2012
Changes that occur in myeloid cells in cancer
MDSC:1-Immature state2-Myeloid origin3-Supress T-cell responses
4-Regulate innate immune responses:modulation the cytokine production ofmacrophages
5-Non-immunological functions:promote angiogenesispromote metastasis
Gabrilovich, Nat Rev Immunol, 2012
Changes that occur in myeloid cells in cancer
• Support tumor growth• suppress anti-tumor immunity
• Support angiogenesis/metastasis• soluble factors
• Potential immunotherapy target
Physiological pathsCancer/Sepsis
Gabrilovich, Nat Rev Immunol, 2009
Inhibition of diff
Stimulation of myelopoiesis
Signaling pathways involved in MDSC expansion
Gabrilovich, Nat Rev Immunol, 2009
Signaling pathways involved in MDSC activation
