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Bone Small Intestine Lymph Node Lung or Lymph Node INVASION METASTASIS Activated Platelets (Protection from NK cell lysis) MMP-2, MMP-9, Other Proteases CAF Breast or Prostate Cancer Cell Breast Cancer Cell Melanoma Cell Carcinoma-associated Fibroblast (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-mediated Tumor 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-γ IFN-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 T reg Treg Treg CD8 + T Cell CD8 + T Cells Dendritic Cell B7 CD4 CD8 TCR-CD3 TCR-CD3 CD28 IL-4 IL-4, IL-5, IL-10, IL-13 IL-4 IL-10 IL-13 TGF-β TGF-β, IL-2 TGF-β, IL-10 TGF-β, IL-10 Th2 Th2 MDSC MDSC CCR7 Draining Lymph Node MHCII MHCI NK NK Apoptotic/Necrotic Bodies M2 Macrophage IL-1β, IL-6, IL-10, IL-12 low Arginase, IL-10, NO Angiogenesis Tumor/Stromal Cell CXCL9 CXCL10 CXCL11 NKT (Type II) TUMOR ESCAPE M2 Macrophage IL-10 IL-12 low TGF-β CCL2 Mast Cells Monocyte Eosinophils CXCR1/2 CXCR4 NFκB HIF-1 HIF-1 IL-8 COX2 MMPs VEGF, CXCL12 VEGF VEGF IL-8 CXCL12 PGE 2 IL-8 CXCL12 PGE 2 EP2 CXCR1/2 CXCR4 EP2 VEGF R2 VEGF R2 M2 Macrophage IL-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, PGE 2 , 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 Neutrophils IL-6, IL-8, VEGF, bFGF TUMOR GROWTH/ANGIOGENESIS bFGF, VEGF Tumor/Stromal Cell Invading Tumor Cell Tumor or Stromal Cell Endothelial Cell CAF CCL19 CCL21 CCL19 CCL21 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, CCR5 CCL3/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 (T reg ) & 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 CXCR2 CXCL1/GROa, CXCL2/GROb, CXCL3/GROg, CXCL5, CXCL8/IL-8 Eosinophils – Angiogenesis CCR3 CCL11/Eotaxin Global [email protected] [email protected] North America TEL 800 343 7475 Europe | Middle East | Africa TEL +44 (0)1235 529449 China [email protected] TEL +86 (21) 52380373 Rest of World bio-techne.com/find-us/distributors TEL +1 612 379 2956 Learn more | rndsystems.com/tumormicroenvironment 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 bio-techne.com rndsystems.com/ TumorMicroenvironment

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Page 1: Rnlu Microenvironmental Regulation of Tumor …...Th0 CD8+ T Cell CD8+ T Cells MHCII MHCI B7 CD4 CD8 Apoptotic/Necrotic Bodies TUMOR REJECTION Perforin-/Granzyme-mediated Tumor Cell

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

Global [email protected] [email protected] North America TEL 800 343 7475 Europe | Middle East | Africa TEL +44 (0)1235 529449 China [email protected] TEL +86 (21) 52380373 Rest of World bio-techne.com/find-us/distributors TEL +1 612 379 2956

Learn more | rndsystems.com/tumormicroenvironment

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

bio-techne.com

rndsystems.com/ TumorMicroenvironment

RnDSy-lu-2945

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