2. Academic Validation
  3. A human mucosal melanoma organoid platform for modeling tumor heterogeneity and exploring immunotherapy combination options

A human mucosal melanoma organoid platform for modeling tumor heterogeneity and exploring immunotherapy combination options

  • Sci Adv. 2023 Oct 27;9(43):eadg6686. doi: 10.1126/sciadv.adg6686.
Lulu Sun 1 2 3,  Xindan Kang 1 2 3,  Houyu Ju 1 2 3,  Chong Wang 1 2 3,  Guizhu Yang 1 2 3,  Rui Wang 1 2 3,  Shuyang Sun 1 2 3
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
  • 2 College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.
  • 3 Shanghai Research Institute of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai 200011, China.
PMID: 37889972 DOI: 10.1126/sciadv.adg6686
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.

Figures
Products