| First Author | Verzella D | Year | 2018 |
| Journal | Cancer Res | Volume | 78 |
| Issue | 5 | Pages | 1275-1292 |
| PubMed ID | 29279355 | Mgi Jnum | J:261892 |
| Mgi Id | MGI:6154475 | Doi | 10.1158/0008-5472.CAN-17-1833 |
| Citation | Verzella D, et al. (2018) GADD45beta Loss Ablates Innate Immunosuppression in Cancer. Cancer Res 78(5):1275-1292 |
| abstractText | T-cell exclusion from the tumor microenvironment (TME) is a major barrier to overcoming immune escape. Here, we identify a myeloid-intrinsic mechanism governed by the NF-kappaB effector molecule GADD45beta that restricts tumor-associated inflammation and T-cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of proinflammatory tumor-associated macrophages (TAM) and intratumoral immune infiltration, thereby diminishing oncogenesis. Our results provide a basis to interpret clinical evidence that elevated expression of GADD45B confers poor clinical outcomes in most human cancers. Furthermore, they suggest a therapeutic target in GADD45beta for reprogramming TAM to overcome immunosuppression and T-cell exclusion from the TME.Significance: These findings define a myeloid-based immune checkpoint that restricts T-cell trafficking into tumors, with potentially important therapeutic implications to generally improve the efficacy of cancer immunotherapy. Cancer Res; 78(5); 1275-92. (c)2017 AACR. |
