Table 3 Biomarkers related to the CD39/CD73/A2AR pathway in cancer

Adenosine gene signature(8 genes)

CXCL1,2,3,5,6,8,PTGS2 and IL-1β recognized as adenosine signature,was positively correlated with adenosine levels.

[96], [133]

Adenosine Signaling Signature(14 genes)

In human cancer, the gene expression of PPARG, CYBB, COL3A1, FOXP3, LAG3, APP, CD81, GPI, PTGS2, CASP1, FOS, MAPK1, MAPK3, CREB1 correlated with A2AR signaling.

[134]

Inflammatory cytokines or molecules

The expression level of CD39 and CD73 are upregulated by various inflammatory cytokines or molecules, including type I interferons, IL-2, IL-1β, IL-6,IL-27, tumour necrosis factor (TNF), prostaglandin E2 or aryl hydrocarbon receptor agonists.

[51]

Tenascin C and EGFR

CD73 directly bind and activate transcin C and EGFR to promote tumor cell growth,adhesiveness and invasiveness.

[135]

Hypoxia-inducible factor (HIF1)

CD39, CD73 and adenosine receptor, including A2A and A2B, are regulated by HIF, which also can inhibit the activity of adenylate kinase and ENTs, inducing the accumulation of adenosine and immunosupressive response in TME.

[73]

p-CREB and p-S6

p-CREB and p-S6 may represent useful pharmacodynamic and efficacy biomarkers of immunotherapies targeting Adenosine.

[92]

TGFβ

In immnue cells, such as T cells, NK cells,myeloid cells,tumour cells,fibroblasts and endothelial cells, the expression level of CD39 and CD73 are upregulated by TGFβ.

[73]

ADA (Adenosine deaminas)

ADA serves as a diagnostic biomarker in lung malignancies. May be valuable to predict which patients may respond better to treatments of blocking adenosine production or signaling.

[136]

LYVE1,PDPN,VEGFC

LYVE1, PDPN and VEGFC positively correlated with the gene expression of ADOA2AR, NT5E and ENTPD1,respectively coding A2AR, CD73, CD39, thereby influencing the adenosine production in several human cancers.

[137]

Intercellulae adhesion molecule 1(ICM-1)

Adenosine suppressed the upregulation of ICAM-1 mediated by IL-18 on human monocytes and it eliminated the production of IL-12, IFN-γ and TNF-α mediated by the enhancement of IL-18.

[138]