Journal ArticleDOI
Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization.
Ana Rita Pombo Antunes,Isabelle Scheyltjens,Francesca Lodi,Julie Messiaen,Asier Antoranz,Johnny Duerinck,Daliya Kancheva,Liesbet Martens,Karen De Vlaminck,Hannah Van Hove,Signe Schmidt Kjølner Hansen,Francesca Maria Bosisio,Koen Van der Borght,Steven De Vleeschouwer,Steven De Vleeschouwer,Raf Sciot,Luc Bouwens,M. Verfaillie,Niels Vandamme,Roosmarijn E. Vandenbroucke,Olivier De Wever,Yvan Saeys,Martin Guilliams,Conny Gysemans,Bart Neyns,Frederik De Smet,Diether Lambrechts,Jo A. Van Ginderachter,Kiavash Movahedi +28 more
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TLDR
This article employed single-cell RNA sequencing and CITE-seq to map the glioblastoma immune landscape in mouse tumors and in patients with newly diagnosed disease or recurrence.Abstract:
Glioblastomas are aggressive primary brain cancers that recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease progression remain poorly understood. Here, we employed single-cell RNA sequencing and CITE-seq to map the glioblastoma immune landscape in mouse tumors and in patients with newly diagnosed disease or recurrence. This revealed a large and diverse myeloid compartment, with dendritic cell and macrophage populations that were conserved across species and dynamic across disease stages. Tumor-associated macrophages (TAMs) consisted of microglia- or monocyte-derived populations, with both exhibiting additional heterogeneity, including subsets with conserved lipid and hypoxic signatures. Microglia- and monocyte-derived TAMs were self-renewing populations that competed for space and could be depleted via CSF1R blockade. Microglia-derived TAMs were predominant in newly diagnosed tumors, but were outnumbered by monocyte-derived TAMs following recurrence, especially in hypoxic tumor environments. Our results unravel the glioblastoma myeloid landscape and provide a framework for future therapeutic interventions.read more
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GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas
Robbie G. Majzner,Sneha Ramakrishna,Kristen W. Yeom,Shabnum Patel,Harshini Chinnasamy,Liora M. Schultz,Rebecca Richards,Li Jiang,Valentin Barsan,Rebecca A Mancusi,Anna Geraghty,Zina Good,Aaron Mochizuki,Shawn M. Gillespie,Angus Toland,Jasia Mahdi,Agnes Reschke,Esther H Nie,Isabelle J. Chau,Maria Caterina Rotiroti,Christopher Mount,Christina Baggott,Sharon Mavroukakis,Emily Egeler,Jennifer Moon,Courtney Erickson,Sean Green,Michael Kunicki,Michelle Fujimoto,Zach Ehlinger,Warren D. Reynolds,Sreevidya Kurra,Katherine E. Warren,Snehit Prabhu,Hannes Vogel,Lindsey Rasmussen,Timothy T. Cornell,Sonia Partap,Paul B. Fisher,Cynthia J. Campen,Mariella G. Filbin,Gerald A. Grant,Bita Sahaf,Kara L. Davis,Steven R. Feldman,Crystal L. Mackall,Michelle Monje +46 more
TL;DR: In this paper , the clinical experience from the first four patients with H3K27M-mutated diffuse midline glioma (DIPG) or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 106 GD2 CAR T cells per kg administered intravenously).
Journal ArticleDOI
GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas
Robbie G. Majzner,Sneha Ramakrishna,Kristen W. Yeom,Shabnum Patel,Harshini Chinnasamy,Liora M. Schultz,Rebecca Richards,Li Jiang,Valentin Barsan,Rebecca A Mancusi,Anna Geraghty,Zina Good,Aaron Mochizuki,Shawn M. Gillespie,Angus Toland,Jasia Mahdi,Agnes Reschke,Esther H Nie,Isabelle J. Chau,Maria Caterina Rotiroti,Christopher Mount,Christina Baggott,Sharon Mavroukakis,Emily Egeler,Jennifer Moon,Courtney Erickson,Sean Green,Michael Kunicki,Michelle Fujimoto,Zach Ehlinger,Warren D. Reynolds,Sreevidya Kurra,Katherine E. Warren,Snehit Prabhu,Hannes Vogel,Lindsey Rasmussen,Timothy T. Cornell,Sonia Partap,Paul B. Fisher,Cynthia J. Campen,Mariella G. Filbin,Gerald A. Grant,Bita Sahaf,Kara L. Davis,Steven A. Feldman,Crystal L. Mackall,Michelle Monje +46 more
TL;DR: In this paper , the clinical experience from the first four patients with H3K27M-mutated diffuse midline glioma (DIPG) or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 106 GD2 CAR T cells per kg administered intravenously).
Journal ArticleDOI
Macrophages as tools and targets in cancer therapy
TL;DR: In this paper , the authors proposed a set of macrophage-targeting strategies that include inhibitors of cytokines and chemokines involved in the recruitment and polarization of tumour-promoting myeloid cells as well as activators of their antitumorigenic and immunostimulating functions.
Journal ArticleDOI
Clinical relevance of tumour-associated macrophages
TL;DR: The diversity of TAMs suggests different possibilities for exploiting particular subsets for therapeutic purposes; as a result, an arsenal of macrophage-targeted agents are currently being tested in the clinic and the inclusion of TAM data in precision oncology molecular tumour boards could become routine practice.
Journal ArticleDOI
Applications of single-cell sequencing in cancer research: progress and perspectives
TL;DR: The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and underlying mechanisms of tumor biological behaviors as mentioned in this paper.
References
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TL;DR: Harmony, for the integration of single-cell transcriptomic data, identifies broad and fine-grained populations, scales to large datasets, and can integrate sequencing- and imaging-based data.
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