Directly reprogrammed NK cells driven by BCL11B depletion enhance targeted immunotherapy against pancreatic ductal adenocarcinoma.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by desmoplastic stroma, immunosuppressive tumor microenvironment (TME), and resistance to standard therapies. Natural killer (NK) cell-based immunotherapies have shown limited efficacy due to impaired persistence, infiltration, and function in PDAC.

Methods

We established a direct reprogramming strategy to generate cytotoxic NK cells (1 F-NKs) by targeting BCL11B, a transcription factor essential for T cell lineage commitment, using shRNA or CRISPR/Cas9 in peripheral blood mononuclear cells (PBMCs). A genome-wide CRISPR/Cas9 screen identified tumor-intrinsic modulators of NK resistance. Functional and in vivo studies assesses the efficacy of 1 F-NKs alone and in combination with mesotheli

SUBMITTER: Kim HS 

PROVIDER: S-EPMC12613755 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature