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HIF-1α Inhibition Improves Anti-Tumor Immunity and Promotes the Efficacy of Stereotactic Ablative Radiotherapy (SABR)
| Content Provider | MDPI |
|---|---|
| Author | Song, Chang W. Kim, Hyunkyung Cho, Hae Un Kim, Mi-Sook Paek, Sun-Ha Park, Heon-Joo Griffin, Robert J. Terezakis, Stephanie Cho, Lawrence Chinsoo |
| Copyright Year | 2022 |
| Description | High-dose hypofractionated radiation such as SABR (stereotactic ablative radiotherapy) evokes an anti-tumor immune response by promoting a series of immune-stimulating processes, including the release of tumor-specific antigens from damaged tumor cells and the final effector phase of immune-mediated lysis of target tumor cells. High-dose hypofractionated radiation also causes vascular damage in tumors, thereby increasing tumor hypoxia and upregulation of hypoxia-inducible factors HIF-1α and HIF-2α, the master transcription factors for the cellular response to hypoxia. HIF-1α and HIF-2α are critical factors in the upregulation of immune suppression and are the master regulators of immune evasion of tumors. Consequently, SABR-induced increase in anti-tumor immunity is counterbalanced by the increase in immune suppression mediated by HIFα. Inhibition of HIF-1α with small molecules such as metformin downregulates immunosuppressive pathways, including the expression of immune checkpoints, and it improves or restores the anti-tumor immunity stimulated by irradiation. Combinations of HIFα inhibitors, particularly HIF-1α inhibitors, with immune checkpoint blocking antibodies may represent a novel approach to boost the overall anti-tumor immune profile in patients and thus enhance outcomes after SABR. |
| Starting Page | 3273 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers14133273 |
| Journal | Cancers |
| Issue Number | 13 |
| Volume Number | 14 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-07-04 |
| Access Restriction | Open |
| Subject Keyword | Cancers Oncology Radiology, Nuclear Medicine and Imaging Sabr Hif-1α Hif-2α Hif-1α Inhibitor Hif-2α Inhibitor Immunotherapy Tumor Hypoxia Immune Checkpoints |
| Content Type | Text |
| Resource Type | Article |
