Single Cell Analysis of Melanoma Reveals a Prognostic Myeloid Cell Signature Associated with Survival in Early and Advanced Melanoma and Response to Immunotherapy in Advanced Melanoma

Introduction: We sought to elucidate myeloid sub-type differences to characterize biology and support therapeutic strategies in melanoma patients with diverse biogeophaphies.

Methods: scRNA-seq of melanoma were combined from 6 datasets with 126 patients. After integration, cells were clustered with scCCESS, using an artificial neural network. We conducted Recursive Partitioning Analysis (RPA), differential expressed gene (DEG) analysis, and pseudobulk comparison. We validated the signature using MuSiC deconvolution on bulk RNA data.

Results: 102,971 single cells from 126 patients generated 6 myeloid cells types. RPA analysis of 42 patients with melanoma brain metastases revealed a myeloid population associated with median survival months (13 vs 32 vs 52, p=0.029). Partial Response (p=0.010) and adjuvant targeted therapy (p=0.036) differed. This cell type was enriched with CLEC10A, AXL, and MHC Class II genes. Signature validated in 42 patients on nivolumab with improved median survival months (13.25 vs 30, p=0.046) and Partial Response (p<0.001). Signature validated in 463 patients in the TCGA with improved median survival months (63 vs 175, p<0.00).

Conclusion: Increased infiltration of a myeloid cell showed improved survival in melanoma brain metastases, advanced melanoma, and early stage melanoma in training and validation datasets. Cell infiltration was also associated with response to nivolumab.