*H-1PV + CTLA-4 (Ipilimumab)/PD-1 (Nivolumab) Immune Checkpoint Blockade*

In order to investigate the immunological effects of H-1PV in combination with ipilimumab and/or nivolumab, a human ex vivo melanoma model was used by Goepfert et al. Similar to the observations made in CRC-derived cells [70], upregulation of immune checkpoints, CTLA-4, PD-1 and PD-L1 in particular, was seen in H-1PV-infected melanoma cells. Yet, the virus potentiated the capacity of melanoma cells to induce iDC maturation in co-culture experiments. Nivolumab and ipilimumab, when added to the treatment scheme, triggered a further increase in the release into the co-culture supernatant of IFN-γ and TNF-α, respectively. Further to this, upon combination with H-1PV, the two ICIs induced stronger CTL activation, compared to virus alone [72]. Combining PV-induced immunogenic oncolysis with CTLA-4 and/or PD-1 blockade allows achieving a double goal, i.e., tumor cell killing and activation of the immune system against the tumor. This triggering of complementary events, centered on tumor destruction and immune-mediated elimination, renders the H-1PV + ICI approach promising for melanoma and other solid tumors' treatment.
