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
5544 - Evaluation of a radiomic signature of CD8 cells in patients treated with immunotherapy-radiotherapy in three clinical trials.
Presenter: Roger Sun
Session: Poster Display session 3
Resources:
Abstract
1117 - Biomarkers predictive of overall survival in advanced cancer patients treated with a peptide-based cancer vaccine.
Presenter: Shigetaka Suekane
Session: Poster Display session 3
Resources:
Abstract
1922 - Expression of PD-L1 in plasma exosomes of NSCLC patients and its associations with PD-L1 expression of corresponding tumor tissues
Presenter: Shaorong Yu
Session: Poster Display session 3
Resources:
Abstract
5495 - Patient’s perspective on digital biomarkers in advanced urologic malignancies
Presenter: Severin Rodler
Session: Poster Display session 3
Resources:
Abstract
3166 - A comprehensive Pan-cancer study of FGFR Aberrations in Chinese cancer patients
Presenter: Yang Gao
Session: Poster Display session 3
Resources:
Abstract
3277 - A Systemic Inflammation Response Index (SIRI) correlates with survival and could be a Predictive Factor for mFOLFIRINOX in Metastatic Pancreatic Cancer (PC)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 3
Resources:
Abstract
2680 - Circulating biomarkers and risk of immune-related adverse events (irAEs) in patients (pts) with advanced Non-small cell lung cancer (aNSCLC) and metastatic melanoma (mMel)
Presenter: Alberto Pavan
Session: Poster Display session 3
Resources:
Abstract
4066 - Breast cancer in young women of Kazakh population depending on germline mutations: results of next-generation sequencing
Presenter: Dilyara Kaidarova
Session: Poster Display session 3
Resources:
Abstract
5514 - Discovery of an ImmunoTranscriptomics signature in blood for early colorectal cancer detection
Presenter: Paolo Angelino
Session: Poster Display session 3
Resources:
Abstract
1595 - Serum Netrin-1 as a Biomarker for Colorectal Cancer Detection
Presenter: Jinzhou Zhu
Session: Poster Display session 3
Resources:
Abstract