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

Research output: Contribution to journalArticle

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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Organoids
Neoplasms
CD8-Positive T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Chordoma
Antibodies
Immunotherapy
Patient Selection
Fluorescent Antibody Technique
Cell Death
Therapeutics
Biomarkers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Patient-derived organoids as a potential model to predict response to PD-1/PD-L1 checkpoint inhibitors. / Scognamiglio, Giosue; De Chiara, Annarosaria; Parafioriti, Antonina; Armiraglio, Elisabetta; Fazioli, Flavio; Gallo, Michele; Aversa, Laura; Camerlingo, Rosa; Cacciatore, Francesco; Colella, Gianluca; Pili, Roberto; de Nigris, Filomena.

In: British Journal of Cancer, 2019.

Research output: Contribution to journalArticle

Scognamiglio, Giosue ; De Chiara, Annarosaria ; Parafioriti, Antonina ; Armiraglio, Elisabetta ; Fazioli, Flavio ; Gallo, Michele ; Aversa, Laura ; Camerlingo, Rosa ; Cacciatore, Francesco ; Colella, Gianluca ; Pili, Roberto ; de Nigris, Filomena. / Patient-derived organoids as a potential model to predict response to PD-1/PD-L1 checkpoint inhibitors. In: British Journal of Cancer. 2019.
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AU - Armiraglio, Elisabetta

AU - Fazioli, Flavio

AU - Gallo, Michele

AU - Aversa, Laura

AU - Camerlingo, Rosa

AU - Cacciatore, Francesco

AU - Colella, Gianluca

AU - Pili, Roberto

AU - de Nigris, Filomena

PY - 2019

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