Abstract 3373
Background
Recently 3D organoid cell cultures have been established for a variety of human cancers. Salivary gland cancer (SGC) is a rare cancer with 22 different subtypes and few treatment options. Our aim is to generate a large repertoire of patient-derived SGC organoids with different phenotypes, which will facilitate pre-clinical and pharmacological studies.
Methods
Fresh tissues of resected primary tumours and/or metastases of SGC patients were collected. Tissues were minced and digested with collagenase type 2 and TrypLE to generate single cells. After washing, the cells were seeded in growth factor reduced Matrigel. Organoid medium, containing Rho kinase inhibitor Y27632, was refreshed twice a week. Viable organoids were characterized by immunohistochemistry and by DNA/RNA sequencing. Moreover, the organoids were used to evaluate various treatments that are or may be relevant for the treatment of SGC.
Results
Between 2016 and 2018 we obtained tissue of 17 SGC patients, of which 16 contained sufficient material for processing: 10 salivary duct carcinoma (SDC), 3 adenoid cystic carcinoma (ACC), 2 muco-epidermoid carcinoma (MEC) and 1 parotid adenocarcinoma not otherwise specified (NOS). For 5 tumors (2 SDC, 2 ACC, 1 adenocarcinoma NOS) viable organoids were established, which could be passaged at least three times. Organoids cultures derived from the other tumours stopped growing after the first passage. Viable organoids showed resemblance with the original primary tumour, based on morphology, protein expression, and growth pattern. Various drugs were tested at a single dose, and showed reduced organoid cell growth compared to untreated controls. Moreover, a dose-response relationship was established for an ALK-positive MEC organoid that was treated with crizotinib. Finally, epithelial-mesenchymal transition was shown in SDC organoids of a primary tumour and a lymph node metastasis of the same patient.
Conclusions
We are the first that have successfully developed and characterized long-term organoid cultures for ACC and SDC. These organoid cell lines will facilitate pre-clinical and pharmacological studies. Other SGC organoid cultures do not grow infinitely, but do provide an in vitro model to study different treatments during initial growth.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Radboud University Medical Center.
Funding
Dutch Salivary Gland Cancer Patient Platform.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4614 - Predictors of Response to Checkpoint Inhibitors in Naïve and Ipilimumab-Refractory Melanoma
Presenter: Domenico Mallardo
Session: Poster Display session 3
Resources:
Abstract
2901 - IFN-γ/IL-10 ratio as predictive biomarker for response to anti-PD-1 therapy in metastatic melanoma patients
Presenter: Emilio Giunta
Session: Poster Display session 3
Resources:
Abstract
2306 - Multiplex Chromogenic Immunohistochemistry (IHC) for Spatial Analysis of Checkpoint-Positive Tumor Infiltrating Lymphocytes (TILs)
Presenter: Scott Ely
Session: Poster Display session 3
Resources:
Abstract
1678 - The role of PD-L1 expression as a predictive biomarker in advanced renal cell carcinoma: a meta-analysis of randomized clinical trials.
Presenter: Alberto Carretero-Gonzalez
Session: Poster Display session 3
Resources:
Abstract
5138 - Radiomic Features as a Non-invasive Biomarker to Predict Response to Immunotherapy in Recurrent or Metastatic Urothelial Carcinoma
Presenter: Kye Jin Park
Session: Poster Display session 3
Resources:
Abstract
5800 - Integrative combination of high-plex digital profiling techniques and cluster analysis to reveal complex immune biology in the tumor microenvironment of mesothelioma
Presenter: Carmen Ballesteros-Merino
Session: Poster Display session 3
Resources:
Abstract
5736 - Predictive factors of response to immunotherapy in 198 patients with metastatic non-microcytic lung cancer (mNSCLC): real world data from 2 university hospitals in Spain
Presenter: Juan Felipe Cordoba Ortega
Session: Poster Display session 3
Resources:
Abstract
5645 - Evaluating Lung CT Density Changes Among Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) Treated with Thoracic Radiotherapy (TRT) alone or TRT Followed by Combined Ipilimumab (IPI) and Nivolumab (NIVO).
Presenter: Kujtim Latifi
Session: Poster Display session 3
Resources:
Abstract
1540 - Immuno-oncology therapy biomarkers differences between polyoma-virus positive and negative Merkel cell carcinomas
Presenter: Zoran Gatalica
Session: Poster Display session 3
Resources:
Abstract
4538 - Can we improve patient selection for phase 1 clinical trials (Ph1) based on Immuno-Oncology score prognostic index (VIO)?
Presenter: Ignacio Matos Garcia
Session: Poster Display session 3
Resources:
Abstract