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

Publication Title

BJC Rep

Authors

Alberto Mendoza-Valderrey, Translational Cancer Immunology and Immunotherapy Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Ethan Dettmann, Translational Cancer Immunology and Immunotherapy Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Douglas Hanes, Providence Research Network, Portland, OR, USA.Follow
Daria Kessler, Bioinformatic Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Ludmila Danilova
Kai Rau, Translational Cancer Immunology and Immunotherapy Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Yueqin Quan
Stacey Stern, Biostatistics Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Garni Barkhoudarian, Neurosurgery Division, Pacific Neuroscience Institute, Santa Monica, CA, USA.Follow
Carlo Bifulco, Earle A. Chiles Research Institute, Genomic and Pathology Department, Portland, OR, USA.Follow
K A Margolin, Melanoma Program, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Steven E Kolker, Dermatopathology Section, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Maria L. Ascierto, Translational Cancer Immunology and Immunotherapy Department, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow

Document Type

Article

Publication Date

5-2-2024

Keywords

california; santa monica; oregon; portland; prn; providence research network; sjci; pni; chiles; genomics

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.

Area of Special Interest

Cancer

Area of Special Interest

Neurosciences (Brain & Spine)

Specialty/Research Institute

Neurosciences

Specialty/Research Institute

Oncology

DOI

10.1038/s44276-024-00060-y