| First Author | Basavaraja R | Year | 2024 |
| Journal | Cell Rep Med | Volume | 5 |
| Issue | 7 | Pages | 101649 |
| PubMed ID | 39019005 | Mgi Jnum | J:354792 |
| Mgi Id | MGI:7736438 | Doi | 10.1016/j.xcrm.2024.101649 |
| Citation | Basavaraja R, et al. (2024) PARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies. Cell Rep Med 5(7):101649 |
| abstractText | Tumor-infiltrating regulatory T cells (TI-Tregs) elicit immunosuppressive effects in the tumor microenvironment (TME) leading to accelerated tumor growth and resistance to immunotherapies against solid tumors. Here, we demonstrate that poly-(ADP-ribose)-polymerase-11 (PARP11) is an essential regulator of immunosuppressive activities of TI-Tregs. Expression of PARP11 correlates with TI-Treg cell numbers and poor responses to immune checkpoint blockade (ICB) in human patients with cancer. Tumor-derived factors including adenosine and prostaglandin E2 induce PARP11 in TI-Tregs. Knockout of PARP11 in the cells of the TME or treatment of tumor-bearing mice with selective PARP11 inhibitor ITK7 inactivates TI-Tregs and reinvigorates anti-tumor immune responses. Accordingly, ITK7 decelerates tumor growth and significantly increases the efficacy of anti-tumor immunotherapies including ICB and adoptive transfer of chimeric antigen receptor (CAR) T cells. These results characterize PARP11 as a key driver of TI-Treg activities and a major regulator of immunosuppressive TME and argue for targeting PARP11 to augment anti-cancer immunotherapies. |
