Colorectal cancer organoids drive hypoxia, TGF-β, and patient-specific diversification of NK cell activation programs.

ABSTRACT:

Background

Colorectal carcinoma exhibits high heterogeneity, comprising subtypes that show poor efficacy of T cell-based immunotherapies, such as programmed cell death protein 1 (PD-1) checkpoint inhibitors. Although natural killer (NK) cells are considered a promising approach for cancer immunotherapy, it remains unclear what molecular mechanisms drive NK cell activation or suppression within the tumor microenvironment. Moreover, limitations in human tumor models that reflect the diversity of individual patient tumors hinder the ability to effectively select patients who would benefit most from NK cell-based therapies.

Methods

Here, we established a co-culture platform of genetically diverse colorectal cancer (CRC) patient-derived organoids (PDOs) with primary allogeneic NK

SUBMITTER: von Kries A 

PROVIDER: S-EPMC12684226 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature