Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases
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s41467-021-25860-5.pdf
Description
Published version
Size
3.5 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Prakadan, Sanjay M
Alvarez-Breckenridge, Christopher A
Markson, Samuel C
Kim, Albert E
Klein, Robert H
Nayyar, Naema
Navia, Andrew W
Kuter, Benjamin M
Kolb, Kellie E
Bihun, Ivanna
Date Issued
2021
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Prakadan, Sanjay M, Alvarez-Breckenridge, Christopher A, Markson, Samuel C, Kim, Albert E, Klein, Robert H et al. 2021. "Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases." Nature Communications, 12 (1).
Version
Final published version
Abstract
AbstractLeptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials. Here, we investigate the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We recover immune and malignant cell types in the CSF, characterize cell behavior changes following ICI, and identify genomic features associated with relevant clinical phenomena. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and demonstrates clinical utility of cell-free and single-cell genomic measurements for LMD research.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Computational and Systems Biology Program
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41467-021-25860-5
