Bone
SmallIntestine
Lymph Node
Lung or Lymph Node
INVASIONMETASTASIS
Activated Platelets(Protection from
NK cell lysis)
MMP-2, MMP-9,Other Proteases
CAF
Breast or ProstateCancer Cell
BreastCancer Cell
MelanomaCell
Carcinoma-associatedFibroblast (CAF)
Developing Primary Tumor
CXCR4
CXCR4
CXCL12
CXCL12
CXCL12
CCL19, CCL21
CCL25
Th0
CD8+ T Cell
CD8+ T Cells
MHCII
MHCI
B7
CD4
CD8
Apoptotic/Necrotic Bodies
TUMOR REJECTION
Perforin-/Granzyme-mediatedTumor Cell Death
Recruitment of Angiogenesis-promoting
Cell Types
Tumor-derived Factors Stimulate Endothelial Cell
Proliferation & Migration
iDC
NK
NKT (Type I)
CCR7
M1 Macrophage
Monocyte
TCR-CD3
TCR-CD3
CD28
IL-12, IFN-γ
IL-12
IL-2, IFN-γ
IFN-γIFN-γ
IL-12, TNF-α, NO
IFN-γ, LPS
Chemokines
Th1
Th1
Draining Lymph Node
CCR7
CCR7
CCR9
CXCR4
CCL19, CCL21
Dendritic Cell
IFN-γ
iDC Accumulation
Th0
Treg
Treg
Treg
CD8+ T Cell
CD8+ T Cells
Dendritic CellB7
CD4
CD8
TCR-CD3
TCR-CD3
CD28
IL-4
IL-4, IL-5, IL-10, IL-13
IL-4IL-10IL-13
TGF-βTGF-β, IL-2
TGF-β, IL-10
TGF-β, IL-10
Th2
Th2
MDSC
MDSC
CCR7
Draining Lymph Node
MHCII
MHCINK
NK
Apoptotic/Necrotic Bodies
M2 MacrophageIL-1β, IL-6, IL-10, IL-12 low
Arginase, IL-10, NO
Angiogenesis
Tumor/Stromal Cell
CXCL9CXCL10CXCL11
NKT (Type II)
TUMOR ESCAPE
M2 MacrophageIL-10
IL-12 lowTGF-βCCL2
Mast Cells
Monocyte
Eosinophils
CXCR1/2CXCR4
NFκB
HIF-1HIF-1
IL-8COX2MMPs
VEGF, CXCL12
VEGFVEGFIL-8
CXCL12
PGE2
IL-8CXCL12
PGE2
EP2CXCR1/2
CXCR4 EP2
VEGF R2VEGF R2
M2 MacrophageIL-1β, IL-6,TNF-α
MMPs, uPA
VEGF, PDGF, bFGF, EGF
bFGF, VEGF
ECM Degradation
Myeloid Progenitor Cell
iDC
IL-8, TNF-α, Osteopontin
TGF-β, MMPs, PGE2, VEGF
VEGF, MMP-9, Oncostatin M
VEGF, bFGF, MMP-9,TNF-α, IL-8, Histamine
CXCL1, CXCL12, IL-6, IL-8, MMPs,PGE
2, VEGF
Extracellular Matrix
CXCL12
NeutrophilsIL-6, IL-8,VEGF, bFGF
TUMOR GROWTH/ANGIOGENESIS
bFGF, VEGF
Tumor/Stromal Cell
Invading Tumor CellTumor or Stromal Cell
Endothelial Cell
CAF
CCL19CCL21
CCL19CCL21
TUMOR-DERIVED CHEMOKINES/CYTOKINES RECRUIT IMMUNE EFFECTOR CELLS THAT MAY PROMOTE TUMOR GROWTH
Cell Type – Tumor-promoting Effects Receptors Tumor-derived Chemokines/Cytokines
Monocytes/Macrophages (Type 2) – Immunosuppression, proliferation & angiogenesis
CCR1, CCR5CCL3/MIP-1a, CCL4/MIP-1b, CCL5/RANTES, CCL8/MCP-2
CCR2 CCL2/MCP-1
M-CSF R M-CSF
Dendritic Cells – Immunosuppression, tumor antigen tolerance, angiogenesis
CCR1, CCR5 CCL3/MIP-1a, CCL4/MIP-1b, CCL5/RANTES
CCR6 CCL20/MIP-3a, b-Defensin
CXCR1, CXCR2 CXCL8/IL-8
CXCR4 CXCL12/SDF-1
Regulatory T Cells (Treg) & Th2 Cells – Immunosuppression
CCR4 CCL17/TARC, CCL22/MDC
Myeloid-derived Suppressor Cells – Immunosuppression, proliferation & angiogenesis
CCR2 CCL2/MCP-1
CXCR2 CXCL5
CXCR4 CXCL12/SDF-1
Mast Cells – Immunosuppression, proliferation & angiogenesis
CCR3 CCL11/Eotaxin
CCR5 CCL5/RANTES
CXCR4 CXCL12/SDF-1
SCF R/c-kit SCF/c-kit Ligand
Neutrophils – Proliferation & angiogenesis
CXCR1 CXCL6/GCP-2, CXCL8/IL-8
CXCR2CXCL1/GROa, CXCL2/GROb, CXCL3/GROg, CXCL5, CXCL8/IL-8
Eosinophils – Angiogenesis
CCR3 CCL11/Eotaxin
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NOTE: This poster conveys a general overview and should be considered neither comprehensive nor definitive. The details of this information are understood to be subject to interpretation. © 2017 Bio-Techne
Microenvironmental Regulation of Tumor Growth & Metastasis
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