Abstract 6865: Single cell analysis of melanoma reveals a prognostic myeloid cell associated with survival in melanoma with brain metastases

Abstract INTRODUCTION: The interface of the innate and adaptive immune system are a critical factor in tumor behavior and responses to immunotherapy with myeloid cell behavior varying widely between various biogeographies. We sought to elucidate myeloid sub-type differences to characterize biology and support therapeutic strategies. METHODS: scRNA-seq of primary skin, acral, and metastatic melanoma were combined from 6 datasets with 126 patients for analysis. After integration, cells were analyzed with scCCESS, which uses an artificial neural network to reduce data and optimize k for k-means clusters. Myeloid clusters with analyzed with Recursive Partitioning Analysis (RPA), differential expressed gene (DEG) analysis, and pseudobulk comparison of RPA groups by gene expression. RESULTS: 102,971 single cells from 126 patients were analyzed to generate a cluster of 15,303 myeloid cells further subjected to clustering generating 6 cell types. RPA analysis of 6 myeloid populations in 46 patients with melanoma brain metastases generated 3 nodes with differing median survival months (17 vs 41 vs 57, p=0.01). There was a trend towards more adjuvant immunotherapy (p=0.057) and targeted therapy (p=0.019) in the worst surviving group. Myeloid type 1 cells showed increased expression of CLEC10A and AXL genes compared to all other cells (adj p = 0.000). Pseudobulk comparison of patient groups of genes showed CLEC10A was significant between all groups (p<0.05). CONCLUSIONS: Although there were no significant differences in neoadjuvant treatment, increased infiltration of CLEC10A myeloid cells showed improved survival in melanoma brain metastases. Targets of current therapies, such as AXL tyrosine kinase, have heterogenous presence across multiple cell types beyond tumors that may impact wide response variances, further study of these populations will have significant impact in both biomarker and therapeutics development. Citation Format: M. Usman Ahmad, Leong Heo, Ramesh V. Nair, Saurabh Sharma, Amanda Kirane. Single cell analysis of melanoma reveals a prognostic myeloid cell associated with survival in melanoma with brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6865.