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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月26日

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  • Marisa Mercadante,
  • Armin Scheben,
  • Jacob Estrada,
  • Jan Savas-Carstens,
  • William Sullivan,
  • Nicholas Housel,
  • Maria Sapar,
  • Tatiana Volpari,
  • Jax Hebner,
  • Tomasz Rusielewicz,
  • Frederick J. Monsma Jr,
  • Stefan Semrau,
  • Yinan Wang,
  • Laura A. Martin

摘要

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.