Single cell analysis of melanoma reveals a prognostic myeloid cell signature associated with survival and response to immunotherapy in advanced melanoma

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B117
Abstract ID: 5921

Presenting Author:
M. Usman Ahmad , Postdoctoral Research Fellow at Stanford Univ. Sch. of Med.

Abstract:

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 myeloid cells of 6 cell types. RPA analysis of 42 patients with melanoma brain metastases revealed a single 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. Myeloid cell type 1 was enriched with CLEC10A, AXL, and MHC Class II genes. 42 patients on nivolumab were used to validate signature with on treatment biopsy with improved median survival months (13.25 vs 30, p=0.046) and Partial Response (p<0.001). 19 patients shifted high infiltration groups during treatment with 11% dropping, 44% increasing, and 47% remaining high.

CONCLUSIONS: Increased infiltration of myeloid cells showed improved survival and treatment response in melanoma brain metastases. Validation of the signature showed an association with nivolumab response and survival.