Brief report on the development of patient-derived lung cancer organoids with keratinizing squamous cell carcinoma morphology

Abstract

IntroductionNovel therapeutic options are urgently required to improve outcomes and survival for patients with lung squamous cell carcinoma (LUSC). In particular, understanding the unique histological features that define LUSC is essential to improving lung cancer mortality. Many pre-clinical models fail to accurately represent intratumour heterogeneity and recapitulate the tumour microenvironment. This is partly responsible for the poor translation of clinical findings to approved therapies. Our objective was to investigate whether patient-derived organoids, replicate the histological morphological, and structural features of keratinizing LUSC, a poor prognostic subtype of lung cancer. MethodsOrganoid cultures were established and maintained from two patients presenting with keratinizing lung squamous cell carcinomas. Immunofluorescent staining of individual organoids and confocal microscopy was performed to confirm expression of tumour markers. Whole organoid domes were fixed, and immunofluorescent staining and imaging was performed to investigate the structural features of the organoid cultures. Findings were compared with histopathological features of the original tumour tissue. ResultsPatient-derived organoids expressed tumour markers specific to the squamous cell carcinoma subtype of non-small cell lung cancer, which were confirmed to be expressed in the parent tissue. Within organoid cultures, keratin pearl structures spontaneously developed, matching the keratinizing pattern demonstrated by hematoxylin and eosin staining of the original tumour. ConclusionsPatient-derived organoids have the capability to replicate key histological features of their parent tumour. This high degree of fidelity makes these 3D models an important and valuable tool for understanding complex tumour biology and as a platform for preclinical drug testing to advance novel therapies into the clinic.