Patient-derived skin tumor organoids with immune cells respond to metformin

Surgery is the primary treatment for skin tumors, but it can result in scarring and distress for patients. Developing alternative therapeutic methods necessitates suitable in vitro models, which are currently limited in accurately representing the in vivo cell types and microenvironment of skin tumors. Here, we present a practical approach for creating patient-derived skin tumor organoids that effectively replicate the histological characteristics and mutational profiles observed in clinical tissues. Utilizing single-cell sequencing, we identified up to 11 distinct cell types within the organoid samples, encompassing various skin system cells and immune cells. Furthermore, we demonstrate the applicability of Dermatofibrosarcoma protuberans (DFSP) organoids for assessing their responses to imatinib and metformin. Our findings reveal that metformin, in contrast to imatinib, can modulate the expression of downstream genes through immune signaling pathways. Our results underscore the ability of DFSP organoids to preserve key features of clinical tissues, including the presence of multiple cell types, especially immune cells. Importantly, our organoids provide a convenient approach for investigating the effects of drugs and elucidating underlying molecular mechanisms.