Oxygenation and A2AR blockade to eliminate hypoxia/HIF-1α-adenosinergic immunosuppressive axis and improve cancer immunotherapy
Autor: | Stephen M. Hatfield, Katarina Halpin-Veszeleiova |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adenosine Receptor Adenosine A2A medicine.medical_treatment Adenosinergic 030226 pharmacology & pharmacy Clinical study 03 medical and health sciences 0302 clinical medicine Cancer immunotherapy Antigens CD Renal cell carcinoma Neoplasms Drug Discovery Immune Tolerance Animals Humans Medicine In patient 5'-Nucleotidase Pharmacology business.industry Apyrase Oxygenation Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Adenosine A2 Receptor Antagonists Blockade Oxygen 030104 developmental biology Cancer research Tumor Hypoxia Immunotherapy medicine.symptom business |
Zdroj: | Current Opinion in Pharmacology. 53:84-90 |
ISSN: | 1471-4892 |
Popis: | The promising results of the first in-human clinical study using A2AR antagonists for treatment of renal cell carcinoma highlight two decades of research into the hypoxia-A2-adenosinergic pathway. Importantly, clinical responses have been observed in patients who previously progressed on anti-PD-1/PDL-1 therapy, emphasizing the clinical importance of targeting A2AR signaling in cancer immunotherapies. Recently, it has been shown that systemic oxygenation weakens all known stages of the hypoxia-A2-adenosinergic axis. Therefore, we advocate the clinical use of systemic oxygenation and oxygenation agents in combination with A2AR blockade to further improve cancer immunotherapies. This approach is expected to completely eliminate the upstream (hypoxia-HIF-1α) and downstream (adenosine-A2AR) stages of the immunosuppressive hypoxia-adenosinergic signaling axis. This might be a necessary strategy to maximize the therapeutic benefits of A2AR antagonists and increase susceptibility of tumors to cancer treatments. |
Databáze: | OpenAIRE |
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