The Discovery of Biochemical & Immunological Mechanisms of the Hypoxia- A2-Adenosinergic Immunosuppression as the Foundation of the Conceptually Novel Immunotherapies of Cancer Using Several Classes of Anti-Hypoxia-A2- Adenosingergic Drugs

Time: 9:10 am
day: Day One


• Highlighting that extracellular adenosine-A2AR/A2BR adenosine receptors-cyclic AMP-PKA axis: provides the “OFF” signal to TCR activated T-Cells and inhibit NK cells and other immune cells, triggers the immunosuppressive transcription of all other known immunosuppressive molecules like PD1 via cAMP Response Element (CRE) and CREB transcription factor

• Discussing that i) inhibition of adenosine-generating enzymes like CD39/CD73 or ii) degrading the extracellular adenosine with adenosine deaminase (ADA) or iii) blockade of A2AR A2B adenosine receptors can promote antitumor immunity

• Understanding how the Hypoxia-HIF-1alpha axis triggers the upregulation of the extracellular adenosine-generating enzymes and is upstream of Adenosine-A2AR/A2BR extracellular receptors to inhibit the anti-tumor immunity

• Exploring that weakening of the Hypoxia in tumors by systemic oxygenation or by oxygenation agents and inhibition of HIF-1alpha by inhibitors will also weaken the immunosuppressive signaling by adenosine-A2AR/A2BR axis downstream and thereby can promote antitumor immunity

• Understanding that even the refractory to all current immunotherapies tumors is expected to be rejected if the blockade of immunological negative regulators (like PD1/CTLA) is combined with anti-Hypoxia-A2-Adenosinergic drugs