1. Cellules myeloides suppressives
M1 – UE9
29 Octobre 2015
Mikael ROUSSEL

2. Hematopoiese Bone Marrow Lymph FL Node Blood Blood Tissues
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
Blood
Blood
Tissues
Gabrilovich, Nat Rev Immunol, 2012

3. Microenvironment and cancerFL
Wolf-Herman, Nat Rev Cancer, 2012
De Visser, Nat Rev Cancer, 2006

4. Microenvironment and cancerFL
Narendra, Inflamm Res, 2013

5. 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)

6. Changes that occur in myeloid cells in cancer
Monocyte
-in blood
-APC ((<DC)
-Phagocytosis
-Cytokine production
-migrate to the tissue
DC :
-APC
-activate T
-link between innate and adaptative
Macrophage
-in tissue
-APC
-Phagocytosis
-Inflammation/anti-inflammation
Gabrilovich, Nat Rev Immunol, 2012

7. Changes that occur in myeloid cells in cancer
MDSC:
1-Immature state
2-Myeloid origin
3-Supress T-cell responses
4-Regulate innate immune responses:
modulation the cytokine production of
macrophages
5-Non-immunological functions:
promote angiogenesis
promote metastasis
Gabrilovich, Nat Rev Immunol, 2012

8. Changes that occur in myeloid cells in cancer
Physiological paths
Cancer/Sepsis
Support tumor growth
suppress anti-tumor immunity
Support angiogenesis/metastasis
soluble factors
Potential immunotherapy target
Gabrilovich, Nat Rev Immunol, 2012

9. Signaling pathways involved in MDSC expansion
Inhibition of diff
Stimulation of myelopoiesis
Gabrilovich, Nat Rev Immunol, 2009

10. Signaling pathways involved in MDSC activation
Gabrilovich, Nat Rev Immunol, 2009