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Monocyte and Macrophage Plasticity in the Tumor Microenvionment · Monocyte and Macrophage...
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Monocyte and Macrophage Plasticity in the Tumor Microenvionment Jason Muhitch, PhD Assistant Professor of Oncology Urology Department MIR 509 Trends in Tumor Immunology October 21 st , 2015
Transcript of Monocyte and Macrophage Plasticity in the Tumor Microenvionment · Monocyte and Macrophage...
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Monocyte and Macrophage Plasticity in the Tumor Microenvionment
Jason Muhitch, PhD Assistant Professor of Oncology
Urology Department
MIR 509 Trends in Tumor Immunology
October 21st, 2015
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Know Your Enemy: Immunosuppressive Functions of Tumor-Associated Macrophages
Ugel et al JCI, 2015
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Know Your Enemy: Identifying Tumor-Associated Macrophages
Murine Human
CD45+ CD68+ CD115+ VCAM+ GR-1-
CXCR9+ CXCR10+ CXCR11+
CD206+
M1 TAM M2 TAM M1 TAM M2 TAM
CD45+ CD68+ CD115+
HLA-DR+ CD205+
CD64+ CD80+
CXCR10+
CD32+ CD163+ PD-L2+
Ugel et al JCI, 2015
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Know Your Enemy: Tumor-Associated Macrophages Impact on Prognosis
Bonapace et al Nature, 2014
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Ugel et al JCI, 2015
Monocyte & Macrophage Plasticity
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Characterization of Monocyte Subsets
Geissmann et al. Immunity, 2003 Cros et al. Immunity 2011 Nahrendorf et al. JEM, 2007 Qian et al. Nature 2011
Nahrendorf et al. JEM, 2007
Classical Non-classical Intermediate
Tissue “patrolling” Less migratory in vitro Higher phagocytic activity
Tissue repair
CCR2-Dependent entry into metastasis
CCR2+ Monocyte (classical) Intratumoral Infiltration Is Associated with Macrophage Accumulation and Poor Prognosis in a Broad Tumor Types
CCR2high CD11Bhigh CD115low
CX3CR1low
CCR2low CD11Blow CD115high
CX3CR1high
CCR2low CD11Blow CD115high
CX3CR1high
Auffrey et al. Science, 2007
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Characterization of Monocyte Subsets
Non-classical (Patrolling) Monocytes CX3CR1
Auffray et al. Science, 2007
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Classical Monocytes Can Also Go Out on Patrol!
Classical monocytes within the liver after focal injury
Dal-Secco et al. JEM 2015
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Classical Monocytes Can Also Go Out on Patrol!
CCR2-/- Classical Monocytes within the liver 4 hours after focal sterile injury
Dal-Secco et al. JEM 2015
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Dal-Secco et al. JEM 2015
CCR2RFP / Cx3cr1GFP
CCR2+ Monocytes can Transition to CX3CR1+ Monocytes
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CCR2+ Monocytes can Transition to CX3CR1+ Monocytes
Dal-Secco et al. JEM 2015
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Changes in Circulating Monocyte Populations Suggest Transition Between Subsets
Particular monocyte subpopulations after anti–M-CSF mAb infusions (for treatment of arthritis).
Mariusz Korkosz et al. Blood 2012;119:5329-5330
Classical
Non-classical
Intermediate
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Changes in Circulating Monocyte Populations Suggest Transition Between Subsets
Saleh et al. Blood 1995
Increased % of CD16+ monocytes after rhM-CSF infusions in healthy subjects
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Myeloid Cells Can Account for More than 50% of Tumor-infiltrating Leukocytes
Movahedi et al Cancer Research, 2010
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Monocyte / Macrophage Plasticity in the Tumor Microenvironment
Movahedi et al Cancer Research, 2010
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Tumor-Associated Macrophages
Franklin et al Science 344, 2014
Inflammatory (Classical) Monocytes
Monocyte / Macrophage Plasticity in the Tumor Microenvironment
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Monocytes Differentiate into TAMs In Vivo
Franklin et al Science 344, 2014
Neutrophils
Inflammatory Monocytes
TAM
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Targeting the CSF-1R to Reduce Intratumoral TAM infiltration
Ries et al Cancer Cell 25, 846-59, 2014
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Targeting the CSF-1R to Reduce Intratumoral TAM infiltration
Ries et al Cancer Cell 25, 846-59, 2014
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Targeting the CSF-1R to Reduce Intratumoral TAM infiltration
Ries et al Cancer Cell 25, 846-59, 2014
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Molecular Profiling Reveals a Tumor-Promoting Phenotype of Monocytes and Macrophages in
Human Cancer Progression
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Fig. 1
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Fig. 1
M2
IFN-γ, TLR agonist IL-4, IL-13, IL-10
IL-12hiIL-23
iNOSROS
CD86 MHC II
Classically Activated
Sica, Journal of Clinical Investigation, March 2012Gabrilovich, Nature reviews, April 2012Martinez et Gordon, F1000PrimeReports,2014
Arg1
CD206 CD163
IL-10hiMMPs
Alternatively Activated
MonocyteM1
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Fig. 2
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Fig. 3
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Fig. 4
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Fig. S4 C
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Fig. 5
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Fig. 6
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Fig. 7
Monocyte and Macrophage�Plasticity in the Tumor MicroenvionmentSlide Number 2Slide Number 3Slide Number 4Slide Number 5Characterization of Monocyte SubsetsCharacterization of Monocyte SubsetsClassical Monocytes Can Also Go Out on Patrol!Classical Monocytes Can Also Go Out on Patrol!Slide Number 10CCR2+ Monocytes can Transition to CX3CR1+ MonocytesChanges in Circulating Monocyte Populations Suggest Transition Between SubsetsChanges in Circulating Monocyte Populations Suggest Transition Between SubsetsSlide Number 14Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Molecular Profiling Reveals a Tumor-Promoting Phenotype of Monocytes and Macrophages in Human Cancer ProgressionSlide Number 22Slide Number 23Slide Number 24Slide Number 25Slide Number 26Slide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31
