Publikationsdatenbank

Establishment and characterization of patient-derived organoids from HNSCC for analyzing mechanisms of radioresistance (2023)

Art

Poster

Autoren

Fisch, A-S. (WE 1)

Pestana, A.

Sachse, V.

Doll, C.

Heiland, M.

Dommerich, S.

Obermüller, T.

Hofmann, V. M.

Klinghammer, K.

Piwonski, I.

Schallenberg, S.

Zips, D.

Tinhofer, I.

Kongress

Human 3D Organ Models : Networking Event

Berlin, 09.05.2023

Quelle

Human 3D organ models : networking event : abstracts — Charité, Universitätsmedizin Berlin (Hrsg.)

Berlin, 2023 — S. 11

Sprache

Englisch

Verweise

URL (Volltext): https://charite3r.charite.de/fileadmin/user_upload/microsites/ohne_AZ/sonstige/charite3r/Meldungen/2023/Poster_abstract_collection_2023_v2.pdf

Kontakt

Institut für Veterinär-Anatomie

Koserstr. 20
14195 Berlin
+49 30 838 75784
anatomie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Achieving personalization in treatment of head and neck squamous cell carcinomas (HNSCC) requiresadequate models. The study aims at the establishment of patient-derived organoids (PDOs) from HNSCC, and the assessment of their potential value in biomarker discovery for radioresistance and screening for radiosensitizing agents
The ethics committee approved this study (EA1/152/10). Tumor tissue from patients with informed consent was collected during diagnostic or curative surgery at the maxillofacial and othorhinolaryngology departments at the Charité. After tissue dissociation and expansion in monolayer cultures, cells were seeded in Matrigel® to form organoids. Statistical analysis was performed with SPSS. Organoid sections were haematoxylin-eosin and immunohistochemically stained for p40, CK5/6 and Ki67. The ex vivo assessment of radiosensitivity was established using 3D cultures of radioresistant
/ -sensitive subclones from the FaDu cell line. The protocol was then applied to PDO models.
Overall efficiency of PDO generation from primary tumor specimen from HNSCC patients was 45%. Histopathological characterization confirmed their SCC-phenotype. The majority of models were from male patients (64%) and actual / former smokers (71%). Neither the tumor localization nor the sample
type (biopsy vs. surgical specimen) was decisive for successful organoid generation. Samples from recurrent or persistent tumors after radiotherapy showed a significant lower engraftment rate (33.3%) compared to treatment naive specimens (80%) (p<0.001). With our irradiation protocol, we were able
to distinguish radiosensitive from resistant FaDu models. Preliminary results from PDOs (n=3) showed a dose-dependent decrease in proliferation, cell-viability (CellTiterGlo®) and clonogenic potential, and a considerable interpatient variability in radiosensitivity.
To our knowledge, this is the largest collection of HNSCC PDO models established so far. Multi-omics characterization is currently ongoing. PDOs might be valuable models to investigate individual responses to radiation therapy and the molecular mechanisms underlying radioresistance. In future
studies, we will also focus on improving organoid engraftment from radioresistant tumors.