| First Author | Bagati A | Year | 2021 |
| Journal | Cancer Cell | Volume | 39 |
| Issue | 1 | Pages | 54-67.e9 |
| PubMed ID | 33385331 | Mgi Jnum | J:300352 |
| Mgi Id | MGI:6501061 | Doi | 10.1016/j.ccell.2020.12.001 |
| Citation | Bagati A, et al. (2021) Integrin alphavbeta6-TGFbeta-SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer. Cancer Cell 39(1):54-67.e9 |
| abstractText | Cancer immunotherapy shows limited efficacy against many solid tumors that originate from epithelial tissues, including triple-negative breast cancer (TNBC). We identify the SOX4 transcription factor as an important resistance mechanism to T cell-mediated cytotoxicity for TNBC cells. Mechanistic studies demonstrate that inactivation of SOX4 in tumor cells increases the expression of genes in a number of innate and adaptive immune pathways important for protective tumor immunity. Expression of SOX4 is regulated by the integrin alphavbeta6 receptor on the surface of tumor cells, which activates TGFbeta from a latent precursor. An integrin alphavbeta6/8-blocking monoclonal antibody (mAb) inhibits SOX4 expression and sensitizes TNBC cells to cytotoxic T cells. This integrin mAb induces a substantial survival benefit in highly metastatic murine TNBC models poorly responsive to PD-1 blockade. Targeting of the integrin alphavbeta6-TGFbeta-SOX4 pathway therefore provides therapeutic opportunities for TNBC and other highly aggressive human cancers of epithelial origin. |
