Viral-Directed Augmentation of Kupffer Cell Cross-Presentation Provokes Antitumor Immunity Against Liver Metastasis.

ABSTRACT: Liver metastasis is associated with poor prognosis and resistance to immune checkpoint inhibitors. Functional modulation of Kupffer cells (KCs) holds promise as an alternative immunotherapeutic approach. Leveraging their capacity to capture circulating virions, an oncolytic virus-based KC-targeting strategy is developed that demonstrated efficacy and safety in treating multifocal liver metastasis. A single intravenous infusion of the M51R mutant vesicular stomatitis virus (VSV-M51R), but not wild-type (WT) VSV, induced significant tumor regression in mouse models of forced liver metastasis, independent of direct oncolysis. The ineffectiveness of VSV-WT is attributed to its induction of massive KC apoptosis, whereas VSV-M51R replicated transiently within KCs without compromising viability.

SUBMITTER: Chen C 

PROVIDER: S-EPMC12533311 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature