Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

Ruochen Du; Shashwat Tripathi; Hinda Najem; Daniel J. Brat; Rimas V. Lukas; Peng Zhang; Amy B. Heimberger

doi:10.3390/cells13100823

Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

Ruochen Du, Shashwat Tripathi, Hinda Najem, Daniel J. Brat, Rimas V. Lukas, Peng Zhang, Amy B. Heimberger^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

3 Scopus citations

Abstract

Macrophages and microglia are professional phagocytes that sense and migrate toward “eat-me” signals. The role of phagocytic cells is to maintain homeostasis by engulfing senescent or apoptotic cells, debris, and abnormally aggregated macromolecules. Usually, dying cells send out “find-me” signals, facilitating the recruitment of phagocytes. Healthy cells can also promote or inhibit the phagocytosis phenomenon of macrophages and microglia by tuning the balance between “eat-me” and “don’t-eat-me” signals at different stages in their lifespan, while the “don’t-eat-me” signals are often hijacked by tumor cells as a mechanism of immune evasion. Using a combination of bioinformatic analysis and spatial profiling, we delineate the balance of the “don’t-eat-me” CD47/SIRPα and “eat-me” CALR/STC1 ligand–receptor interactions to guide therapeutic strategies that are being developed for glioblastoma sequestered in the central nervous system (CNS).

Original language	English (US)
Article number	823
Journal	Cells
Volume	13
Issue number	10
DOIs	https://doi.org/10.3390/cells13100823
State	Published - May 2024

Funding

A.B.H. serves on the advisory board of Caris Life Sciences and the WCG Oncology Advisory Board; receives royalty and milestone payments from DNAtrix for the licensing of the patent \u201CBiomarkers and combination therapies using oncolytic virus and immunomodulation\u201D (no. 11,065,285); is supported by research grants from Alnylam and AbbVie; and receives consulting fees from Novocure and Istari Oncology. She additionally has the granted patents titled \u201CmiRNA for treating cancer and for use with adoptive immunotherapies\u201D (no. 9,675,633) and \u201CConcurrent chemotherapy and immunotherapy\u201D (no. 9,399,662), with patent pending, \u201CLow-intensity ultrasound combination cancer therapies\u201D (International Applications PCT/US2022/019435 and US 63/158,642). R.V.L. serves on the advisory boards for AstraZeneca, Bayer, Cardinal Health, Merck, Novartis, Novocure, and Servier; serves at speakers\u2019 bureau for Merck and Novocure; receives research support (drug only) from BMS; and receives honoraria for editing from EBSCO, Elsevier, Medlink Neurology, and Oxford University Press. A.B.H. is supported by NIH grants CA120813, NS120547, NS122857, NS124594, CA275430, CA221747, and CA272639.

Keywords

gliomas
immune checkpoint blockade
myeloid cells

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cells13100823

Cite this

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title = "Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation",

abstract = "Macrophages and microglia are professional phagocytes that sense and migrate toward “eat-me” signals. The role of phagocytic cells is to maintain homeostasis by engulfing senescent or apoptotic cells, debris, and abnormally aggregated macromolecules. Usually, dying cells send out “find-me” signals, facilitating the recruitment of phagocytes. Healthy cells can also promote or inhibit the phagocytosis phenomenon of macrophages and microglia by tuning the balance between “eat-me” and “don{\textquoteright}t-eat-me” signals at different stages in their lifespan, while the “don{\textquoteright}t-eat-me” signals are often hijacked by tumor cells as a mechanism of immune evasion. Using a combination of bioinformatic analysis and spatial profiling, we delineate the balance of the “don{\textquoteright}t-eat-me” CD47/SIRPα and “eat-me” CALR/STC1 ligand–receptor interactions to guide therapeutic strategies that are being developed for glioblastoma sequestered in the central nervous system (CNS).",

keywords = "gliomas, immune checkpoint blockade, myeloid cells",

author = "Ruochen Du and Shashwat Tripathi and Hinda Najem and Brat, {Daniel J.} and Lukas, {Rimas V.} and Peng Zhang and Heimberger, {Amy B.}",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

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doi = "10.3390/cells13100823",

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volume = "13",

journal = "Cells",

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AU - Du, Ruochen

AU - Tripathi, Shashwat

AU - Najem, Hinda

AU - Brat, Daniel J.

AU - Lukas, Rimas V.

AU - Zhang, Peng

AU - Heimberger, Amy B.

PY - 2024/5

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N2 - Macrophages and microglia are professional phagocytes that sense and migrate toward “eat-me” signals. The role of phagocytic cells is to maintain homeostasis by engulfing senescent or apoptotic cells, debris, and abnormally aggregated macromolecules. Usually, dying cells send out “find-me” signals, facilitating the recruitment of phagocytes. Healthy cells can also promote or inhibit the phagocytosis phenomenon of macrophages and microglia by tuning the balance between “eat-me” and “don’t-eat-me” signals at different stages in their lifespan, while the “don’t-eat-me” signals are often hijacked by tumor cells as a mechanism of immune evasion. Using a combination of bioinformatic analysis and spatial profiling, we delineate the balance of the “don’t-eat-me” CD47/SIRPα and “eat-me” CALR/STC1 ligand–receptor interactions to guide therapeutic strategies that are being developed for glioblastoma sequestered in the central nervous system (CNS).

AB - Macrophages and microglia are professional phagocytes that sense and migrate toward “eat-me” signals. The role of phagocytic cells is to maintain homeostasis by engulfing senescent or apoptotic cells, debris, and abnormally aggregated macromolecules. Usually, dying cells send out “find-me” signals, facilitating the recruitment of phagocytes. Healthy cells can also promote or inhibit the phagocytosis phenomenon of macrophages and microglia by tuning the balance between “eat-me” and “don’t-eat-me” signals at different stages in their lifespan, while the “don’t-eat-me” signals are often hijacked by tumor cells as a mechanism of immune evasion. Using a combination of bioinformatic analysis and spatial profiling, we delineate the balance of the “don’t-eat-me” CD47/SIRPα and “eat-me” CALR/STC1 ligand–receptor interactions to guide therapeutic strategies that are being developed for glioblastoma sequestered in the central nervous system (CNS).

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KW - immune checkpoint blockade

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Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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