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Updated: Jun 8, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Immunogenomics and spatial proteomic mapping highlight distinct neuro-immune architectures in melanoma vs.
Alberto Mendoza-Valderrey1, Ethan Dettmann1, Douglas Hanes2
1Translational Cancer Immunology and Immunotherapy Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.
Background:
Brain metastases (BrMs) are a devastating complication of solid tumours. A better understanding of BrMs biology is needed to address their challenging clinical management.
Methods:
Immunogenomic and digital spatial analyses were applied to interrogate the peripheral blood and tumour specimens derived from 53 unique patients with BrMs originating from different solid tumours.
Results:
At craniotomy time, patients with melanoma-derived brain metastasis (MBM) displayed in the periphery lower neutrophil-lymphocyte ratio (NLR) compared to non-melanoma-derived brain metastasis (non-MBM). Regardless of the primary tumour source, higher NLR was associated with reduced overall survival (OS). Tumour MicroEnviroment genomic evaluations revealed higher expression of genes identifying NK, CD8 and B cells in MBM vs. non-MBM. Moreover, MBM patients with longer OS displayed increased CD8+ cell infiltration. Spatial proteomic analysis further highlighted enriched infiltration of CD8+ cells, antigen-presenting cells, T-cell agonists and B cells in MBM. Conversely, increased expression of genes and proteins associated with neurodevelopment, cell-cell adhesion and neutrophil infiltration were observed in non-MBM.
Conclusions:
These findings reveal an increased immunogenicity of MBM vs non-MBM and highlight the presence of a unique neuro-immune interplays in MBM vs non-MBM, suggesting that a balance between neuro-immune architectures might be associated with diverging clinical outcome of patients with BrMs.
