Targeting the A₃ adenosine receptor to treat cytokine release syndrome in cancer immunotherapy

Figures & data

Table 1 Adenosine anti-inflammatory effect is A₃AR mediated

	Study	Findings
Vincenzi et al 2013^Citation42	Pulsed electromagnetic fields increased the anti-inflammatory effect of A2a and A3 adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts.	An in vitro model of inflammatory bone and joint disorder – A3AR activation by adenosine was efficacious in decrease of some of the most relevant pro- inflammatory cytokines release such as IL-6 and IL-8.
Antonioli et al 2010^Citation43	The blockade of adenosine deaminase ameliorates chronic experimental colitis through the recruitment of adenosine A2a and A3 receptors.	Inflammatory model of colitis – ADA inhibitors and A3AR antagonists induced a decrease in TNF-α and IL-6. By blocking ADA, adenosine accumulates in the inflamed environment and binds to its receptors. Cytokine inhibition was counteracted by antagonizing the A3AR or A2aAR (but not A1AR and A2bAR), demonstrating that at least part of the adenosine effect was A3AR mediated.
Baharav et al 2002^Citation44	Suppression of experimental zymosan-induced arthritis by intraperitoneal administration of adenosine.	The administration of adenosine significantly reduced serum TNF-α levels and resulted in remarkable clinical benefit in an animal model of zymosan- induced arthritis. Since adenosine is a small molecule with a half-life time of <20 seconds, rapidly metabolizing to inosine, it cannot be utilized as a drug candidate.^Citation28
Madi et al 2007^Citation61	Overexpression of A3 adenosine receptor in peripheral blood mononuclear cells in rheumatoid arthritis: involvement of nuclear factor-kappa B in mediating receptor level.	Overexpression of A3AR was found in PBMC of RA patients. Receptor upregulation was induced by inflammatory cytokines controlling the expression of the A3AR transcription factor NF-kappa B.
Gessi et al 2004^Citation65	Expression of A3 adenosine receptors in human lymphocytes: upregulation in T cell activation.	An in-depth investigation of A3 receptors in human lymphocytes demonstrates that, under activating conditions, they are upregulated and may contribute to the effects triggered by adenosine.

Abbreviations: A₃AR, A₃ adenosine receptor; ADA, adenosine deaminase; IL, interleukin; NF-kappaB, nuclear factor κB; PBMC, peripheral blood mononuclear cells; RA, rheumatoid arthritis; TNF-α, tumor necrosis factor-α.

VincenziFTargaMCorciuloCPulsed electromagnetic fields increased the anti-inflammatory effect of A2A and A3 adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblastsPLoS One201385e6556123741498

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