Immunogenomics and spatial proteomic mapping highlight distinct neuro-immune architectures in melanoma vs. non-melanoma-derived brain metastasis

Alberto Mendoza-Valderrey; Ethan Dettmann; Douglas Hanes; Daria M Kessler; Ludmila Danilova; Kai Rau; Yueqin Quan; Stacey Stern; Garni Barkhoudarian; Carlo Bifulco; Kim Margolin; Steven Kolker; Maria L Ascierto

doi:10.1038/s44276-024-00060-y

Immunogenomics and spatial proteomic mapping highlight distinct neuro-immune architectures in melanoma vs. non-melanoma-derived brain metastasis

BJC Rep. 2024 May 2;2(1):38. doi: 10.1038/s44276-024-00060-y.

Authors

Affiliations

¹ Translational Cancer Immunology and Immunotherapy Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.
² Providence Research Network, Portland, OR, USA.
³ Bioinformatic Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.
⁴ Division of Quantitative Science, Department of Oncology, School of Medicine at Johns Hopkins, Baltimore, MD, USA.
⁵ Biostatistics Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.
⁶ Neurosurgery Division, Pacific Neuroscience Institute, Santa Monica, CA, USA.
⁷ Earle A. Chiles Research Institute, Genomic and Pathology Department, Portland, OR, USA.
⁸ Melanoma Program, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.
⁹ Dermatopathology Section, Providence Saint John's Health Center, Santa Monica, CA, USA.
¹⁰ Translational Cancer Immunology and Immunotherapy Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA. ml.ascierto@gmail.com.

Abstract

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.

Abstract

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