Patient-derived organoids as a potential model to predict response to PD-1/PD-L1 checkpoint inhibitors

Giosue Scognamiglio, Annarosaria De Chiara, Antonina Parafioriti, Elisabetta Armiraglio, Flavio Fazioli, Michele Gallo, Laura Aversa, Rosa Camerlingo, Francesco Cacciatore, Gianluca Colella, Roberto Pili, Filomena de Nigris

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Abstract

Selection of cancer patients for treatment with immune checkpoint inhibitors remains a challenge due to tumour heterogeneity and variable biomarker detection. PD-L1 expression in 24 surgical chordoma specimen was determined immunohistochemically with antibodies 28-8 and E1L3N. The ability of patient-derived organoids to detect treatment effects of nivolumab was explored by quantitative and qualitative immunofluorescence and FACS analysis. The more sensitive antibody, E1L3N (ROC = 0.896, p = 0.001), was associated with greater tumour diameters (p = 0.014) and detected both tumour cells and infiltrating lymphocytes in 54% of patients, but only 1–15% of their cells. Organoids generated from PD-L1-positive patients contained both tumour cells and PD-1/CD8-positive lymphocytes and responded to nivolumab treatment with marked dose-dependent diameter reductions of up to 50% and increased cell death in both PD-L1-positive and negative organoids. Patient-derived organoids may be valuable to predict individual responses to immunotherapy even in patients with low or no immunohistochemical PD-L1 expression.

Original languageEnglish
JournalBritish Journal of Cancer
DOIs
Publication statusPublished - 2019

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Scognamiglio, G., De Chiara, A., Parafioriti, A., Armiraglio, E., Fazioli, F., Gallo, M., Aversa, L., Camerlingo, R., Cacciatore, F., Colella, G., Pili, R., & de Nigris, F. (2019). Patient-derived organoids as a potential model to predict response to PD-1/PD-L1 checkpoint inhibitors. British Journal of Cancer. https://doi.org/10.1038/s41416-019-0616-1