Mechanistic Justifications of Systemic Therapeutic Oxygenation of Tumors to Weaken the Hypoxia Inducible Factor 1α-Mediated Immunosuppression
| Autor: | Stephen M. Hatfield, Michail V. Sitkovsky, Katarina Veszeleiova, Joe Steingold, Jyothi Sethuraman |
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| Rok vydání: | 2019 |
| Předmět: |
Tumor microenvironment
biology business.industry Adenosine receptor signaling pathway medicine.medical_treatment Immunosuppression Acquired immune system 03 medical and health sciences 0302 clinical medicine Immune system Cancer immunotherapy Immunity MHC class I Cancer research biology.protein Medicine 030212 general & internal medicine business |
| Zdroj: | Advances in Experimental Medicine and Biology ISBN: 9783030127336 |
| Popis: | Long-term studies of anti-pathogen and anti-tumor immunity have provided complementary genetic and pharmacological evidence for the immunosuppressive and immunomodulatory effects of Hypoxia-HIF-1α and adenosine-mediated suppression via the A2A adenosine receptor signaling pathway (Hypoxia-A2A-adenosinergic). This pathway is life saving when it protects inflamed tissues of vital organs from collateral damage by overactive anti-pathogen immune cells or enables the differentiation of cells of adaptive immunity. However, the Hypoxia-A2A-adenosinergic immunosuppression can also prevent tumor rejection by inhibiting the anti-tumor effects of T and NK cells. In addition, this suppressive pathway has been shown to mask tumors due to the hypoxia-HIF-α-mediated loss of MHC Class I molecules on tumor cells. It is suggested that it will be impossible to realize the full anti-tumor capacities of current cancer immunotherapies without simultaneous administration of anti-Hypoxia-A2A-Adenosinergic drugs that inactivate this tumor-protecting mechanism in hypoxic and adenosine-rich tumors. |
| Databáze: | OpenAIRE |
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