Table 1.

Overview of the involvement of A2AR in cancers and autoimmune diseases.

	A2AR expression	Major finding	Reference
Cancers
Colorectal cancer	Highly expressed in tumor tissues	High expressions of A2aR and PD‐L1 were associated with a poor prognosis of colorectal cancer	[48, 49]
Gastric cancer	Up‐regulation on gastric cancer tumor tissue and CD8+ T cells	A2AR expression was associated with TNM stage, lymph node metastasis, distant metastasis and poor prognosis	[50, 51]
Renal cell carcinoma	Up‐regulated in tumor tissue	A2AR expression was associated with renal cell carcinoma metastasis, resistance to immune‐targeted therapy, and shortened OS	[52, 53]
Breast cancer	Up‐regulated in the cancer tissues	The activation of A2AR increased the proliferation and invasion ability of breast cancer cells, and was associated with tumor growth and metastasis	[29]
Melanoma	The expression levels of A2aR and A2BR are higher than those of A1AR and A3AR in human melanoma cell lines	Adenosine can enhance the proliferation of melanoma cells through A2AR, and on the other hand, the activation of A2AR may also induce cell death	[54, 55]
Autoimmune diseases
Rheumatoid arthritis	Up‐regulated in peripheral leukocytes in RA patients	Activation of A2AR inhibits NF‐κB signaling pathway and IL‐1, IL‐6 and TNF production	[56]
Ankylosing spondylitis	Up‐regulated on lymphocytes and monocyte‐derived macrophages in AS patients	A2AR activation inhibits the activation of NF‐κB and suppressed TNF, IL‐1β, IL‐6, MMP‐1, MMP‐3 production but increased IL‐23 mRNA expression	[56, 57]
Systemic lupus erythematosus	Higher levels of A2AR expression were found on T cells in SLE patients	Activation of A2AR inhibits inflammatory cytokines (IFN‐α, TNF, IL‐2, IL‐6, IL‐1β) and increases the anti‐inflammatory cytokine IL‐10 release	[58, 59]
Inflammatory bowel diseases	A2AR mRNA was increased in the colonic mucosal tissue of patients with active Crohn's disease	A2AR activation reduce inflammatory cytokine release, decreased the infiltration of lymphocytes, thereby reduced intestinal mucosal inflammation	[60, 61]
Type 1 diabetes	Increased in coronary smooth muscle and endothelial cells in type I diabetic mice	Activation of A2AR regulates coronary blood flow, inhibits NETosis, and exerts a protective effect in a T1DM model	[62, 63]
Multiple sclerosis	Up‐regulated in lymphocytes of MS patients	Inconsistent roles of A2AR appear in the EAE models	[64, 65, 66]

Abbreviations: EAE, experimental autoimmune encephalomyelitis; TNM, tumor node metastasis.