| First Author | Zheng N | Year | 2022 |
| Journal | Cancer Cell | Volume | 40 |
| Issue | 9 | Pages | 973-985.e7 |
| PubMed ID | 36027915 | Mgi Jnum | J:337585 |
| Mgi Id | MGI:7336627 | Doi | 10.1016/j.ccell.2022.08.001 |
| Citation | Zheng N, et al. (2022) Induction of tumor cell autosis by myxoma virus-infected CAR-T and TCR-T cells to overcome primary and acquired resistance. Cancer Cell 40(9):973-985.e7 |
| abstractText | Cytotoxicity of tumor-specific T cells requires tumor cell-to-T cell contact-dependent induction of classic tumor cell apoptosis and pyroptosis. However, this may not trigger sufficient primary responses of solid tumors to adoptive cell therapy or prevent tumor antigen escape-mediated acquired resistance. Here we test myxoma virus (MYXV)-infected tumor-specific T (T(MYXV)) cells expressing chimeric antigen receptor (CAR) or T cell receptor (TCR), which systemically deliver MYXV into solid tumors to overcome primary resistance. In addition to T cell-induced apoptosis and pyroptosis, tumor eradication by CAR/TCR-T(MYXV) cells is also attributed to tumor cell autosis induction, a special type of cell death. Mechanistically, T cell-derived interferon gamma (IFNgamma)-protein kinase B (AKT) signaling synergizes with MYXV-induced M-T5-SKP-1-VPS34 signaling to trigger robust tumor cell autosis. CAR/TCR-T(MYXV)-elicited autosis functions as a type of potent bystander killing to restrain antigen escape. We uncover an unexpected synergy between T cells and MYXV to bolster solid tumor cell autosis that reinforces tumor clearance. |
