An oncolytic virus-delivered TGFβ inhibitor overcomes the immunosuppressive tumor microenvironment.

ABSTRACT: While checkpoint blockade immunotherapies have widespread success, they rely on a responsive immune infiltrate; as such, treatments enhancing immune infiltration and preventing immunosuppression are of critical need. We previously generated αPD-1 resistant variants of the murine HNSCC model MEER. While entirely αPD-1 resistant, these tumors regress after single dose of oncolytic vaccinia virus (VV). We then generated a VV-resistant MEER line to dissect the immunologic features of sensitive and resistant tumors. While treatment of both tumor types induced immune infiltration and IFNγ, we found a defining feature of resistance was elevation of immunosuppressive cytokines like TGFβ, which blunted IFNγ signaling, especially in regulatory T cells. We engineered VV to express a genetically encod

SUBMITTER: DePeaux K 

PROVIDER: S-EPMC10407786 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature