Abstract 3860: Metastasis score: A powerful tool to determine the metastatic potential and the appropriate adjuvant therapy of melanoma

Metastasis is the onerous challenge in the prognosis of melanoma patients. Accurately predicting the metastatic potential of non-metastatic melanoma (NMM) and determining effective postoperative adjuvant therapy for inhibiting metastasis remain uncertain. In this study, we conducted comprehensive analyses of melanoma metastases using bulk and single-cell RNA sequencing data, enabling the construction of a metastasis score (MET score) through multiple machine-learning algorithms. The reliability and robustness of the MET score were validated by various in vitro and in vivo assays. Our findings revealed a distinct molecular landscape in metastatic melanoma summarized by the enrichment of metastasis-related pathways, complex cell-cell communication, and heightened infiltration of pro-angiogenic tumor-associated macrophages compared to NMM. Importantly, patients of the high MET score group exhibited poorer prognoses and immunosuppressive microenvironment, featuring increased infiltration of regulatory T cells and decreased infiltration of CD8+ T cells, compared to the low MET score patient group. Expression of PD-1 was markedly higher in patients of low MET scores. Anti-PD-1 (aPD-1) therapy profoundly affected antitumor immunity activation and metastasis inhibition in these patients. In summary, our study demonstrates the effectiveness of the MET score in predicting melanoma metastatic potential. For patients with low MET scores, aPD-1 monotherapy may be a potential treatment strategy to inhibit metastasis. Patients with high MET scores may benefit from combination therapies. Citation Format: Kangjie Shen, Chuanyuan Wei, Jianying Gu. Metastasis score: A powerful tool to determine the metastatic potential and the appropriate adjuvant therapy of melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3860.