Target   Treatment   Tumor model   Outcome of adenosine axis blockade depends on presence/unhindered function of   Impact on the TME
CD73  ➣ mAbs:
TY/23 (368, 378–384)
2C5 IgG2a (384)
Oleclumab (385)
AD2 (386)
➣ Pharmacologic inhibitor:
APCP (378, 379, 381, 383, 384, 387–389)  ➣ Breast:
4T1.2 (368, 382, 383)
E0771 (368)
LM3a (386)
MDA-MB-231a (386)
➣ Melanoma:
B16-SIY (378)
B16-F10 (379, 381, 384, 387, 389)
K1735 (381)
LWT1 (384)
➣ Ovarian:
ID8 (378, 388)
➣ Prostate:
TRAMP-C1 (380)
RM-1 (382)
➣ Colon:
CT26 (385)
MC38-OVA (382)
➣ Fibrosarcoma: MCA-induced (380, 382)
➣ Lymphoma:
EG7 (379)  ➣ Primary tumor expansionrate ↓ (368, 378–382, 385, 387, 389)
Host CD73 (387)
A2AR on hematopoietic cells (368)
T cells, NK cells or B cells (368)
T cells (381)
CD8 T cells (380)
IFN-γ (382)
IL-17A (381)
Partially retained inmice depleted of B cells (381)
Retained in perforin KO mice (382)
➣ Metastasis formation ↓ (368, 379, 380, 384, 386)
Retained against tumor cells with significantly reduced CD73 (386)
Host CD73 (380)
MDSCs (384)
Retained in mice depleted of T cells or NK cells (380)
Retained in SCID mice lacking T cells, NK cells and functional B cells (386)
Host FcRIV (384)
FcR binding capacity (384)
Independent of the capacity to suppress CD73 catalytic activity (384, 386)
➣ Survival↑ (378, 382, 384, 388)  ↑ CD8+ T cells (381, 385, 389)↑ tumor-specific CD8+ T cells (382)↓ CD73 on CD4+/CD8+ T cells (382, 384)↑ B cells (381)↓ Tregs (389)↑ MDSCs (384)↓ CD73 on MDSCs (384)↑ IFN-γ, TNF-α, IL-17A (381)↓ Ki67+ cells (381)↓ Bcl-2+ cells (381)↓ Microvessel density (383)↓ VEGF (383)
CD39  ➣ mAb:
9-8B (390)
➣ Pharmacologic inhibitor:
POM-1 (391)  ➣ Melanoma: B16-F10 (391)
➣ Colon: MCA38 (391)
➣ Sarcoma: IGN-SRC- 004a (390)  ➣ Primary tumor expansion rate ↓ (391)
Host CD39 (391)
➣ Survival ↑ (390)
Retained in NOG mice lacking T cells, B cells, NK cells and functional macrophages (390)
CD38  ➣ mAb:
NIMR-5 (96)
➣ Pharmacologic inhibitor:
Rhein (96)  ➣ Lung:
344SQ (96)
LLC-JSP (96)
531LN3 (96)  ➣ Primary tumor expansion rate ↓ (96)
CD8+ T cells (96)  ↑ CD8+ T cells (96)↑ CD44hiCD62Llo CD8+ T cells (96)↓ PD-1+TIME3+ CD8+ T cells (96)↓ Tregs (96)↓ MDSCs (96)
Intratumoral hypoxia  Respiratory hyperoxia (60% O2) (9, 293)  ➣ Breast: 4T1 (293)
➣ Melanoma:
B16 (9)
B16-F10 (293)
CL8-1 (9)
➣ Fibrosarcoma: MCA205 (9, 293)  ➣ Primary tumor expansion rate ↓ (9)
➣ Metastasis formation ↓ (293)
CD4 > CD8 > NK cells (293)
Host A2AR (293)
Independent of 60%O2-induced ROS production (293)
➣ Survival ↑ (9, 293)   ↓ Hypoxia (9, 293)↓ HIF- 1α (9)↑ FHL-1, FIH-1, VHL (HIF- 1α inhibitors) (9)↓ CD39, CD73, A2AR, A2BR, COX-2 mRNA (9)↓ extracellular adenosine (9)↑ CD8+, CD69+, CD44+ cells (293)↓ Tregs (293)↑ IL-2, IL-12, CXCL9, CXCL10, CXCL11 mRNA (293)↓ TGF-β (293)↓ FOXP3 in Tregs (293)↓ CD39, CD73, CTLA-4 on Tregs (293)↑ MHC class I on tumor cells (9)↓ VEGF, VEGF mRNA (9)↓ Microvessel density (9)
A2AR  ➣ Antagonists:
ZM241385 (38, 54)
ZM241365 (389)
SCH58261 (54, 292, 384, 392–394)
FSPTP (395)
CPI-444 (396)
PBF-509 (397)  ➣ Breast:
4T1.2 (292)
➣ Melanoma:
B16-F10 (292, 384, 389, 394, 395, 397)
CL8-1 (38)
BRAFV600E-PTEN-deficient mice (393)
LWT1 (393)
➣ Colon:
CT26 (396)
MC38 (396)
➣ NSCLC: PC9a (54)
➣ Bladder: MB49 (395)
➣ HNSCC: Tgfbr1/Pten double KO (392)
➣ Fibrosarcoma: MCA205 (397)  ➣ Primary tumor expansion rate ↓ (38, 54, 389, 392, 393, 396)
T cells (38)
Retained in NUDE micelackingT cells (54)
➣ Metastasis formation ↓ (292, 384, 393, 394, 397)
Tumor CD73 (292, 394)
Host A2AR (292)
T cells, B cells or NK cells (292)
Perforin (292)
➣ Survival↑ (384, 396)
CD8 T cells > NK cells (394)  ↓ CD8+, CD4+ T cells (395)↑ CD8+ T cells (389, 392, 393)↑ CD69 on CD8+ T cells (393)↓ A2AR+ CD8+ T cells (392)↑ IFN-γ+ CD8+ T cells (392)↑ T-bet, 41-BB in/on CD44+CD8+ T cells (396)↑ IFN-γ, TNF-α production by CD8+ T cells (392)↑ stimulation-induced IFN-γ/TNF-αproduction by CD8+ T cells (396)↑ NK cells (393, 395)↑ GzB+ NK cells (292)↓ Tregs (389, 392, 393)↓ PD-1, LAG3, FOXP3 on Tregs (396)↓ A2AR+ Tregs (392)↓ FOXP3 (392)
A2BR  ➣ Antagonists:
PSB1115 (292, 315, 359, 398)
ATL-801 (399)  ➣ Breast:
4T1.2 (292, 359, 368, 399)
E0771 (359)
➣ Melanoma:
B16-F10 (292, 315, 359, 398)
LWT1 (359)
➣ Bladder: MB49 (399)  ➣ Primary tumor expansion rate ↓ (315, 398, 399)
Mature T cells (399)
T cells (398)
Host A2BR (399)
Host CXCR3 (399)
Retained in A2AR−/− mice (399)
Retained in mice depleted of MDSCs but lost upon adoptive transfer of MDSCs (398)
➣ Metastasis formation ↓ (292, 359, 368)
Tumor CD73 (292)
Retained in RAG−/−cγ−/− mice lacking T cells, B cells and NK cells (292)
Retained in mice depleted of T cells, NK cells D11c+ DCs or macrophages (359)
➣ Survival↑ (359)
Tumor A2BR (359)
Retained in mice depleted of T cells or NK cells (359)  ↑ CD8+ T cells (315, 398)↑ CXCR3+ T cells (399)↑ NKT cells (315, 398)↓ MDSCs (315, 398)↑IFN-γ, CXCL10 mRNA (399)↑ IFN-γ, TNF-α, GzB (398)↓ MCP-1, IL-10 (398)↓ VEGF (315)↓ Microvessel density (315)