Induction of tumor cell autosis by myxoma virus-infected CAR-T and TCR-T cells to overcome primary and acquired resistance

Cancer Cell. 2022 Sep 12;40(9):973-985.e7. doi: 10.1016/j.ccell.2022.08.001. Epub 2022 Aug 25.


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 (TMYXV) 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-TMYXV cells is also attributed to tumor cell autosis induction, a special type of cell death. Mechanistically, T cell-derived interferon γ (IFNγ)-protein kinase B (AKT) signaling synergizes with MYXV-induced M-T5-SKP-1-VPS34 signaling to trigger robust tumor cell autosis. CAR/TCR-TMYXV-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.

Keywords: CAR-T cells; acquired resistance; autosis; myxoma virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunotherapy, Adoptive
  • Myxoma virus* / physiology
  • Neoplasms*
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen* / genetics
  • T-Lymphocytes


  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen