| First Author | Gao J | Year | 2016 |
| Journal | Cell | Volume | 167 |
| Issue | 2 | Pages | 397-404.e9 |
| PubMed ID | 27667683 | Mgi Jnum | J:253298 |
| Mgi Id | MGI:6109135 | Doi | 10.1016/j.cell.2016.08.069 |
| Citation | Gao J, et al. (2016) Loss of IFN-gamma Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy. Cell 167(2):397-404.e9 |
| abstractText | Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-gamma, which is a critical cytokine for host immune responses. However, the role of IFN-gamma signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here, we demonstrate that patients identified as non-responders to anti-CTLA-4 (ipilimumab) have tumors with genomic defects in IFN-gamma pathway genes. Furthermore, mice bearing melanoma tumors with knockdown of IFN-gamma receptor 1 (IFNGR1) have impaired tumor rejection upon anti-CTLA-4 therapy. These data highlight that loss of the IFN-gamma signaling pathway is associated with primary resistance to anti-CTLA-4 therapy. Our findings demonstrate the importance of tumor genomic data, especially IFN-gamma related genes, as prognostic information for patients selected to receive treatment with immune checkpoint therapy. |
