Related Experiment Video
Updated: Jul 12, 2025
Author Spotlight: Recreating Melanoma Complexity with Patient-Derived Organoids for Immunotherapy Evaluation
Published on: September 6, 2024
A human mucosal melanoma organoid platform for modeling tumor heterogeneity and exploring immunotherapy combination
Lulu Sun1,2,3, Xindan Kang1,2,3, Houyu Ju1,2,3
1Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Abstract:
Mucosal melanoma (MM), an aggressive rare subtype of melanoma, is distinct from cutaneous melanoma and has poor prognoses. We addressed the lack of cell models for MM by establishing 30 organoids of human oral MM (OMM), which retained major histopathological and functional features of parental tumors. Organoid groups derived from chronologically or intratumorally distinct lesions within the same individual displayed heterogeneous genetics, expression profiles, and drug responses, indicating rapid tumor evolution and poor clinical response. Furthermore, transcriptome analysis revealed receptor tyrosine kinases (RTKs) signaling, particularly NGFR, a nerve growth factor receptor, was significantly up-regulated in OMMs and organoids from patients resistant to anti-programmed cell death protein 1 (anti-PD-1) therapy. Combining anti-PD-1 with anlotinib (a phase 2 multitarget RTK inhibitor for OMM) or NGFR knockdown enhanced the effective activity of immune cells in organoid-immune cell coculture systems. Together, our study suggested that OMM organoids serve as faithful models for exploring tumor evolution and immunotherapy combination strategies.
