Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25860-5
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Funding
- National Cancer Institute [P30-CA14051]
- Damon Runyon Cancer Research Foundation [81-15]
- Breast Cancer Research Foundation [ELFF-17001]
- Merck Sharp Dohme Corp
- Bristol-Myers Squibb
- Melanoma Research Alliance
- Ben and Catherine Ivy Foundation
- Searle Scholars Program
- Beckman Young Investigator Program
- Pew-Stewart Scholars Program for Cancer Research
- Sloan Fellowship in Chemistry
- NIH [1U54CA217377, 2P01AI039671, 5U24AI118672, 1U2CCA23319501, 5R01CA227156-02, 1R21CA220253-0A01, 1R01CA244975-01]
- Bill and Melinda Gates Foundation
- Susan G. Komen
- Wong Family Award
- DF/HCC Lung Cancer Program Developmental Research Project Award in Lung Cancer Research
- Dana-Farber Institutional Research Support
- Tawingo Fund
- NIH/NINDS R25
- American Brain Tumor Association
- AANS/CNS Joint Section on Tumors
- Demetra fund of the Hellenic Women's Association
- Koch Institute for Integrative Cancer Research at MIT
- Dana-Farber/Harvard Cancer Center
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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.
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.
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