Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases

Autor: Viktor A. Adalsteinsson, Jackson Stocking, Megha Subramanian, Alex K. Shalek, Samuel Markson, Ivanna Bihun, Joana L. Mora, Andrew W. Navia, Scott L. Carter, Priscilla K. Brastianos, Daniel P. Cahill, Nancy Wang, Eudocia Q. Lee, Christopher Alvarez-Breckenridge, Kellie E. Kolb, Sanjay M. Prakadan, Marc H. Wadsworth, Denisse Rotem, Jeffrey W. Miller, Ryan J. Sullivan, Robert H. Klein, Michael White, Benjamin M. Kuter, Alexander Kaplan, Ugonma Chukwueke, Albert E. Kim, Mia Bertalan, Brian A. Shaw, Naema Nayyar
Rok vydání: 2021
Předmět:
Male
Oncology
medicine.medical_treatment
Programmed Cell Death 1 Receptor
Cell
General Physics and Astronomy
Phases of clinical research
Cancer immunotherapy
CD8-Positive T-Lymphocytes
Metastasis
Transcriptome
Meningeal Neoplasms
Tumor Microenvironment
CTLA-4 Antigen
Immune Checkpoint Inhibitors
Multidisciplinary
Brain Neoplasms
Genomics
Middle Aged
Gene Expression Regulation
Neoplastic
Nivolumab
medicine.anatomical_structure
Female
Immunotherapy
Single-Cell Analysis
Cell-Free Nucleic Acids
Meningeal Carcinomatosis
Adult
medicine.medical_specialty
Science
Antibodies
Monoclonal
Humanized
Article
General Biochemistry
Genetics and Molecular Biology
Interferon-gamma
Immune system
Internal medicine
medicine
Humans
Author Correction
Aged
Tumor microenvironment
business.industry
Cancer
General Chemistry
medicine.disease
Ipilimumab
Survival Analysis
CNS cancer
business
Complication
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021)
ISSN: 2041-1723
Popis: Leptomeningeal 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.
Leptomeningeal disease (LMD) is a serious complication of metastatic solid tumors with a poor prognosis. Here, by using single-cell RNA sequencing of cerebrospinal fluid, the authors report genomic and immune correlates of response to immunotherapy in two cohorts of patients with LMD treated with immune checkpoint inhibitors.
Databáze: OpenAIRE
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