Programmable bacteria synergize with PD-1 blockade to overcome cancer cell-intrinsic immune resistance mechanisms.

ABSTRACT: Interferon-γ (IFN-γ) is a potent cytokine critical for response to immunotherapy, yet conventional methods to systemically deliver this cytokine have been hindered by severe dose-limiting toxicities. Here, we engineered a strain of probiotic bacteria that home to tumors and locally release IFN-γ. A single intratumoral injection of these IFN-γ-producing bacteria was sufficient to drive systemic tumor antigen-specific antitumor immunity, without observable toxicity. Although cancer cells use various resistance mechanisms to evade immune responses, bacteria-derived IFN-γ overcame primary resistance to programmed cell death 1 (PD-1) blockade via activation of cytotoxic Foxp3^-CD4⁺ and CD8⁺ T cells. Moreover, by activating natural killer (NK) cells, bacteria-deri

SUBMITTER: Li F 

PROVIDER: S-EPMC11984541 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature