Table 3 Two-way stimulatory immune checkpoint induces tissue and systemic inflammation (mouse study)

 CD40:CD40L

CD40^−/−APOE^−/−

AS

Spleen memory CD4⁺/CD8⁺ TC↓

20100871

2007

Rag1^−/−

Lung CA

Tumor Th1/Th17↑, Treg/Th2↓ to CD40 agonist

25651850

2015

 CD137:CD137L

APOE^−/−

AS

Lesion CD3⁺/CD8⁺ TC↑ to CD137 agonist

18285570

2008

NSG

Osteosarcoma

Ameliorate CAR TC exhaustion to CD137

25939063

2015

 CD134:CD134L

LDLR^−/−

AS

Lesion CD3⁺ TC↓ to α-OX40L

24068673

2013

C57BL/6

Mammary CA

Blood effector/memory TC↑ to α-OX40+Dribbles

27874054

2016

 CD27:CD70

CD70^−/−LDLR^−/−

AS

Spleen Treg↓

27786334

2017

CD27^−/−

Solid tumor

Spleen Treg↓, tumor CD3⁺ TC infiltration↑

22628427

2012

 CD30:CD30L

LDLR^−/−

AS

Adventitial CD3⁺ TC↓ to α-CD30L

23087358

2012

C57BL/6

Fibrosarcoma

CD30⁺ Vδ TC drives cancer progression

27384869

2016

 GITR:GITRL

LDLR^−/−GITRL^TG

AS

Lymph node Terg/effector memory CD4⁺ TC↑

27444204

2016

 CD40:CD40L

CD40^−/−APOE^−/−

AS

Blood Ly6C⁺ MC↓, aorta M1 MØ↓

20100871

2007

KPC

Pancreatic CA

Tumor M1 MØ↑ to CD40 agonist

21436454

2011

 CD137:CD137L

CD137^−/−APOE^−/−

AS

Aorta CD11b⁺ MC/MØ↓

25059229

2014

C57BL/6

Liver CA

Tumor iNOS-positive MØ↑ to CD137 agonist

24789574

2014

 CD134:CD134L

OX40L^−/−APOE^−/−

AS

VEGF-induced angiogenesis↓

20584752

2010

C57BL/6

Sarcoma

Tumor M1 MØ↑ to CD134 agonist

22578109

2012

 CD27:CD70

CD70^TG APOE^−/−

AS

Circulating MC viability↓

20505312

2010

SCID

Lymphoma

Delete MØ reduce survival to α-CD70

17038522

2007

 CD30:CD30L

LDLR^−/−

AS

Lesion MØ/BC no affect

23087358

2012

SCID

Lymphoma

Delete MØ reduce survival to α-CD30

17909075

2007

GITR:GITRL

C57BL/6

Liver tumor

Tumor M1 MØ↑ to GITR agonist+sunitinib

26239999

2016