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 language | English |
|---|---|
| Journal | British Journal of Cancer |
| DOIs | |
| Publication status | Published - 2019 |
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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 journal › Article
}
TY - JOUR
T1 - Patient-derived organoids as a potential model to predict response to PD-1/PD-L1 checkpoint inhibitors
AU - Scognamiglio, Giosue
AU - De Chiara, Annarosaria
AU - Parafioriti, Antonina
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
Y1 - 2019
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85074705717&partnerID=8YFLogxK
U2 - 10.1038/s41416-019-0616-1
DO - 10.1038/s41416-019-0616-1
M3 - Article
C2 - 31666667
AN - SCOPUS:85074705717
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
ER -