cellules myeloides suppressives m1 – ue9 29 octobre 2015 mikael roussel...

Cellules myeloides suppressives

M1 – UE929 Octobre 2015Mikael ROUSSEL

mikael.roussel@chu-rennes.fr

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