American Association for Cancer Research
Browse
cir-21-0870_supplementary_figures_suppsf1-sf15.pdf (8.62 MB)

Supplementary Figure from Microenvironmental Landscape of Human Melanoma Brain Metastases in Response to Immune Checkpoint Inhibition

Download (8.62 MB)
journal contribution
posted on 2023-04-04, 01:44 authored by Christopher Alvarez-Breckenridge, Samuel C. Markson, Jackson H. Stocking, Naema Nayyar, Matt Lastrapes, Matthew R. Strickland, Albert E. Kim, Magali de Sauvage, Ashish Dahal, Juliana M. Larson, Joana L. Mora, Andrew W. Navia, Robert H. Klein, Benjamin M. Kuter, Corey M. Gill, Mia Bertalan, Brian Shaw, Alexander Kaplan, Megha Subramanian, Aarushi Jain, Swaminathan Kumar, Husain Danish, Michael White, Osmaan Shahid, Kristen E. Pauken, Brian C. Miller, Dennie T. Frederick, Christine Hebert, McKenzie Shaw, Maria Martinez-Lage, Matthew Frosch, Nancy Wang, Elizabeth Gerstner, Brian V. Nahed, William T. Curry, Bob Carter, Daniel P. Cahill, Genevieve Marie Boland, Benjamin Izar, Michael A. Davies, Arlene H. Sharpe, Mario L. Suvà, Ryan J. Sullivan, Priscilla K. Brastianos, Scott L. Carter
Supplementary Figure from Microenvironmental Landscape of Human Melanoma Brain Metastases in Response to Immune Checkpoint Inhibition

Funding

Damon Runyon Cancer Research Foundation

Melanoma Research Alliance

Breast Cancer Research Foundation

NIH

NCI

Adelson Medical Research Foundation

Melanoma Foundation

History

ARTICLE ABSTRACT

Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity in the MBM TME, most notably multiple distinct neutrophil states, including an IL8-expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. In addition, we observed significant relationships between intracranial T-cell phenotypes and the distribution of T-cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data identify unique features of the MBM TME that may represent potential targets to improve clinical outcomes for patients with MBM.

Usage metrics

    Cancer Immunology Research

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC