Large scale quantification of natural killer cell-induced apoptosis in patient-derived organoids reveals intratumoral response heterogeneity

NPJ Precis Oncol. 2025 Dec 26. doi: 10.1038/s41698-025-01251-7. Online ahead of print.

ABSTRACT

Intratumoral heterogeneity drives immunotherapy resistance, hindering clinical efficacy. Functional assays that capture heterogeneous responses to immunotherapies remain limited. Here, we present a 3D live imaging assay using patient-derived ovarian cancer organoids to quantify natural killer (NK) cell-induced apoptosis across hundreds of individual organoids. Our assay reveals inter- and intratumor response heterogeneity and detects rare populations unresponsive to NK cytotoxicity, enabling the study of subclonal immune responses and underlying mechanisms.

PMID:41453973 | DOI:10.1038/s41698-025-01251-7