Large scale quantification of natural killer cell-induced apoptosis in patient-derived organoids reveals intratumoral response heterogeneity
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.
Authors
- Maria L. Sapar
- L. A. Martin (ORCID: https://orcid.org/0000-0003-2677-1025)
- Tatiana Volpari
- Tomasz Rusielewicz
- Armin Scheben (ORCID: https://orcid.org/0000-0002-2230-2013)
- Marisa Mercadante
- Jacob Estrada
- Stefan Semrau (ORCID: https://orcid.org/0000-0002-4245-2246)
- Frederick J. Monsma (ORCID: https://orcid.org/0000-0002-5711-5883)
- William J. Sullivan (ORCID: https://orcid.org/0000-0003-1823-8642)
- Jan Savas-Carstens
- Nicholas Housel
- Jax Hebner
- Yinan Wang
Institutions
- Stevens Institute of Technology (US)
- Jackson State Community College (US)
- New York Stem Cell Foundation (US)
- Courant Institute of Mathematical Sciences (US)
- The San Raffaele Telethon Institute for Gene Therapy (IT)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-12-26
- DOI
- https://doi.org/10.1038/s41698-025-01251-7
- Citations
- 1
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.80