Characterizing spatial immune architecture in metastatic melanoma using high-dimensional multiplex imaging

作者：Joel Eliason, Santhoshi Krishnan, Yasunari Fukuda, Matías A. Bustos, Dan Winkowski, Sung-Nam Cho, Akshay Basi, Regan Baird, Elizabeth A. Grimm, Michael A. Davies, Dave S.�B. Hoon, Arvind Rao, Jared K. Burks, Sühendan Ekmekçioğlu · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1560778 · 被引用次数：9 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved survival for patients with metastatic melanoma, yet many experienceresistance due to immunosuppressive mechanisms within the tumor immune microenvironment (TIME). Understanding how the spatial architecture of immune and inflammatory components changes across disease stages may reveal novel prognostic biomarkers and therapeutic targets. Methods: = 248) metastatic tumors. Using imaging mass cytometry (IMC) and multiplex immunofluorescence (mIF), we characterized the phenotypic, functional, and spatial properties of the TIME. Cellular neighborhoods were defined by inflammatory marker expression, and spatial interactions between immune and tumor cells were quantified using nearest-neighbor functions (G-cross). Associations with survival were assessed using Cox proportional hazards models with robust variance estimation. Results: Stage IV tumors exhibited a distinct immune landscape, with increased CD74- and MIF-enriched inflammatory neighborhoods and reduced iNOS-associated regions compared to Stage III. Cytotoxic T lymphocytes (CTLs) and tumor cells were more prevalent in Stage IV TIME, while B cells and NK cells were depleted. Spatial analysis revealed that CTL-Th cell, NK-T cell, and B-NK cell interactions were linked to improved survival, whereas macrophage aggregation and excessive B-Th cell clustering in inflammatory regions correlated with worse outcomes. Organ-specific analyses showed that CTL i...