6533b851fe1ef96bd12a8daf

RESEARCH PRODUCT

Studying Tumor-ReacTive T Cells: A Personalized Organoid Model.

Ugur Sahin

subject

0301 basic medicineLymphocyteT-LymphocytesTranslation (biology)Cell BiologyBiologyCoculture TechniquesArticleOrganoids03 medical and health sciences030104 developmental biologymedicine.anatomical_structureNeoplasmsGeneticsmedicineCancer researchOrganoidMolecular MedicineCoculture TechniqueHumansValue (mathematics)

description

Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer – T cell interactions for individual patients, and understand determinants of responsiveness, are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses for epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich for tumor-reactive T cells from peripheral blood of patients with mismatch repair deficient colorectal cancer and non-small cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.

10.1016/j.stem.2018.08.015https://pubmed.ncbi.nlm.nih.gov/30100188