VEGFR | MET | AXL

INCREASED IMMUNOSUPPRESSIVE CELLS IN THE TUMOR MICROENVIRONMENT

INHIBIT THE ANTI-TUMOR IMMUNE RESPONSE12,13

VEGFR, MET, and AXL signaling promotes angiogenesis as well as infiltration and expansion of immunosuppressive cell types, including MDSCs and Tregs12-22

GAS-6 produced in the tumor microenvironment binds to AXL, polarizing macrophages toward an immunosuppressive phenotype23,24

VEGFR | MET | AXL

PD-1 AND PD-L1 IMMUNE CHECKPOINT SIGNALING

RESULTS IN SUPPRESSION OF CYTOTOXIC T CELLS4

VEGF upregulates PD-1 expression on cytotoxic T cells, which suppresses their activity25

MET and AXL signaling increases PD-L1expression on tumor cells3,26-28

VEGFR | MET | AXL | PD-1

SIMULTANEOUSLY BLOCKING MULTIPLE RECEPTORS IS A STRATEGY TO:29-34

• OVERCOME TREATMENT RESISTANCE• REDUCE IMMUNOSUPPRESSION• STRENGTHEN THE ANTI-TUMOR IMMUNE RESPONSE

DYSREGULATED IMMUNE SIGNALING CONTRIBUTES TO IMMUNOSUPPRESSION, TUMOR IMMUNE EVASION, AND TUMOR CELL SURVIVAL1-4

Activated dendritic cell

Dendritic cell

Macrophage

Tumor

MDSC

VEGFR | AXL

IMPAIRED DENDRITIC CELL FUNCTION

LEADS TO REDUCED CYTOTOXIC T-CELL ACTIVITY1,5-7

Dendritic cell maturation is suppressed by VEGFR signaling1,7,8

Dendritic cell function is suppressed by AXL signaling9-11

Cytotoxic T cell

Cytotoxic T cell

VEGFR

MET

TAM family (AXL, TYRO3, MER)

PD-1 and PD-L1

Treg

Treg

Blood vessel

Modulating the Anti-tumor Immune Response

VEGFR | MET | AXL

INCREASED IMMUNOSUPPRESSIVE CELLS IN THE TUMOR MICROENVIRONMENT

INHIBIT THE ANTI-TUMOR IMMUNE RESPONSE12,13

VEGFR, MET, and AXL signaling promotes angiogenesis as well as infiltration and expansion of immunosuppressive cell types, including MDSCs and Tregs12-22

GAS-6 produced in the tumor microenvironment binds to AXL, polarizing macrophages toward an immunosuppressive phenotype23,24

VEGFR | MET | AXL

PD-1 AND PD-L1 IMMUNE CHECKPOINT SIGNALING

RESULTS IN SUPPRESSION OF CYTOTOXIC T CELLS4

VEGF upregulates PD-1 expression on cytotoxic T cells, which suppresses their activity25

MET and AXL signaling increases PD-L1expression on tumor cells3,26-28

VEGFR | MET | AXL | PD-1

SIMULTANEOUSLY BLOCKING MULTIPLE RECEPTORS IS A TREATMENT STRATEGY TO:29-34

• OVERCOME TREATMENT RESISTANCE• REDUCE IMMUNOSUPPRESSION• STRENGTHEN THE ANTI-TUMOR IMMUNE RESPONSE

DYSREGULATED IMMUNE SIGNALING CONTRIBUTES TO IMMUNOSUPPRESSION, TUMOR IMMUNE EVASION, AND TUMOR CELL SURVIVAL1-4

Activated dendritic cell

Dendritic cell

Macrophage

Tumor

MDSC

VEGFR | AXL

IMPAIRED DENDRITIC CELL FUNCTION

LEADS TO REDUCED CYTOTOXIC T-CELL ACTIVITY1,5-7

Dendritic cell maturation is suppressed by VEGFR signaling1,7,8

Dendritic cell function is suppressed by AXL signaling9-11

Cytotoxic T cell

Cytotoxic T cell

VEGFR

MET

TAM family (AXL, TYRO3, MER)

PD-1 and PD-L1

Treg

Blood vessel

Modulating the Anti-tumor Immune Response

© 2020 Exelixis VV-MED-01063 v2.0 21Aug2020GAS-6=growth arrest-specific 6; MDSC=myeloid-derived suppressor cell; PD-1=programmed cell death-1; PD-L1=programmed death ligand-1; Treg=regulatory T cell; VEGF=vascular endothelial growth factor; VEGFR=vascular endothelial growth factor receptor.

REFERENCES

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