Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma

Kacper A. Walentynowicz; Dalit Engelhardt; Simona Cristea; Shreya Yadav; Ugoma Onubogu; Roberto Salatino; Melanie Maerken; Cristina Vincentelli; Aashna Jhaveri; Jacob Geisberg; Thomas O. McDonald; Franziska Michor; Michalina Janiszewska

Cell Reports (Mar 2023)

Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma

Kacper A. Walentynowicz,
Dalit Engelhardt,
Simona Cristea,
Shreya Yadav,
Ugoma Onubogu,
Roberto Salatino,
Melanie Maerken,
Cristina Vincentelli,
Aashna Jhaveri,
Jacob Geisberg,
Thomas O. McDonald,
Franziska Michor,
Michalina Janiszewska

Affiliations

Kacper A. Walentynowicz: Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular Medicine, Scripps Research, Jupiter, FL, USA
Dalit Engelhardt: Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA
Simona Cristea: Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Department of Medical Oncology, Harvard Medical School, Boston, MA, USA
Shreya Yadav: Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular Medicine, Scripps Research, Jupiter, FL, USA
Ugoma Onubogu: Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular Medicine, Scripps Research, Jupiter, FL, USA; The Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA, USA
Roberto Salatino: Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular Medicine, Scripps Research, Jupiter, FL, USA; The Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA, USA
Melanie Maerken: Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular Medicine, Scripps Research, Jupiter, FL, USA
Cristina Vincentelli: Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA
Aashna Jhaveri: Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA
Jacob Geisberg: Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA
Thomas O. McDonald: Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA
Franziska Michor: Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA; The Ludwig Center at Harvard, Boston, MA, USA; Corresponding author
Michalina Janiszewska: Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technologies, Jupiter, FL, USA; Department of Molecular Medicine, Scripps Research, Jupiter, FL, USA; The Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 3
p. 112235

Abstract

Read online

Summary: Glioblastoma (GBM) is the most aggressive brain tumor, with a median survival of ∼15 months. Targeted approaches have not been successful in this tumor type due to the large extent of intratumor heterogeneity. Mosaic amplification of oncogenes suggests that multiple genetically distinct clones are present in each tumor. To uncover the relationships between genetically diverse subpopulations of GBM cells and their native tumor microenvironment, we employ highly multiplexed spatial protein profiling coupled with single-cell spatial mapping of fluorescence in situ hybridization (FISH) for EGFR, CDK4, and PDGFRA. Single-cell FISH analysis of a total of 35,843 single nuclei reveals that tumors in which amplifications of EGFR and CDK4 more frequently co-occur in the same cell exhibit higher infiltration of CD163+ immunosuppressive macrophages. Our results suggest that high-throughput assessment of genomic alterations at the single-cell level could provide a measure for predicting the immune state of GBM.

CP: Cancer

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords