A bispecific Clec9A-PD-L1 targeted type I interferon profoundly reshapes the tumor microenvironment towards an antitumor state.

ABSTRACT: Despite major improvements in immunotherapeutic strategies, the immunosuppressive tumor microenvironment remains a major obstacle for the induction of efficient antitumor responses. In this study, we show that local delivery of a bispecific Clec9A-PD-L1 targeted type I interferon (AcTaferon, AFN) overcomes this hurdle by reshaping the tumor immune landscape.Treatment with the bispecific AFN resulted in the presence of pro-immunogenic tumor-associated macrophages and neutrophils, increased motility and maturation profile of cDC1 and presence of inflammatory cDC2. Moreover, we report empowered diversity in the CD8⁺ T cell repertoire and induction of a shift from naive, dysfunctional CD8⁺ T cells towards effector, plastic cytotoxic T lymphocytes together with increased p

SUBMITTER: Van Lint S 

PROVIDER: S-EPMC10685570 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature