Treatment with oncolytic vaccinia virus infects tumor-infiltrating regulatory and exhausted T cells.

These findings suggest that OVs are capable of infecting more than just malignant cells after treatment, and that this infection may be an important part of the OV mechanism. We found that exhausted CD8+ T cells and regulatory CD4+ T cells were preferentially infected at early timepoints after treatment and subsequently died. When cell death in T cells was mitigated, mice responded poorly to VV treatment, suggesting that the deletion of these populations is critical to the therapeutic response to VV.