Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma.

摘要: Oncolytic viruses induce local tumor destruction and inflammation. Whether virotherapy can also overcome immunosuppression in noninfected areas is under debate. To address this question, we have explored immunologic effects of oncolytic herpes simplex (oHSVs) a genetically engineered mouse model isocitrate dehydrogenase (IDH) wild-type glioblastoma, the most common malignant primary brain adults. Our recapitulates genomics, diffuse infiltrative growth pattern, extensive macrophage-dominant human glioblastoma. Infection with an oHSV that was armed UL16-binding protein 3 (ULBP3) expression cassette inhibited distant absence viral spreading (abscopal effect) yielded accumulation activated macrophages T cells. There abscopal synergism oHSVULBP3 anti-programmed cell death 1 (anti-PD-1) against distant, uninfected areas; albeit consistent clinical trials patients monotherapy anti-PD-1 ineffective our model. Arming ULBP3 led to upregulation antigen processing presentation gene sets myeloid The cognate receptor NKG2D, however, not present on cells, suggesting noncanonical mechanism action ULBP3. Overall, myeloid-dominant, anti-PD-1-sensitive effect warrants further investigation IDH