Spatial transcriptomics reveals the immunomodulatory activities of an oncolytic adenovirus armed with a type I interferon in a replication-permissive immunocompetent pancreatic cancer model

Oncolytic adenoviruses (OAds) are emerging as a promising class of viro-immunotherapy. Here, we focused on a replication-competent OAd armed with a type I interferon (OAd-IFN) and assessed its immunological activities in a replication-permissive, immunocompetent Syrian hamster pancreatic cancer model. Our spatial transcriptomic analysis revealed the critical role of locally expressed type I IFN in the immunomodulatory activities of OAd-IFN in the tumor microenvironment. Hamsters bearing HP-1 pancreatic cancer tumors were treated intratumorally with OAd-IFN or its counterpart OAd expressing firefly luciferase (OAd-Luc). Based on the tumor volumes, hamsters treated with either of the OAds were assigned to the following criteria: Responder with a tumor volume less than 500 mm^3 and Less-responder with a tumor volume of 500-1500 mm^3. Two of four hamsters in the OAd-IFN group were classified as Responder while the other two in the OAd-IFN group and all four hamsters in the OAd-Luc group were classified as Less-responder. From them, one of the OAd-Luc, two of the OAd-IFN (Less-responder), and one of the OAd-IFN (Responder) samples were analyzed by spatial transcriptomics (Visium Spatial Gene Expression, 10x Genomics).