Skip to main content
main-content

25.03.2020 | Laboratory Investigation

Repolarized macrophages, induced by intermediate stereotactic dose radiotherapy and immune checkpoint blockade, contribute to long-term survival in glioma-bearing mice

Zeitschrift:
Journal of Neuro-Oncology
Autoren:
Alexander M. Stessin, Mariano Guardia Clausi, Zirun Zhao, Hong Lin, Wei Hou, Zhao Jiang, Timothy Q. Duong, Stella E. Tsirka, Samuel Ryu
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s11060-020-03459-y) contains supplementary material, which is available to authorized users.
Alexander M. Stessin and Mariano Guardia Clausi have contributed equally to the work.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Introduction

Glioblastoma multiforme (GBM) is a deadly brain tumor with a short expected median survival, despite current standard-of-care treatment. We explored the combination of intermediate stereotactic dose radiation therapy and immune checkpoint inhibitor therapy as a novel treatment strategy for GBM.

Methods

Glioma xenograft-bearing mice were exposed to high dose brain-directed radiation (10 Gy single exposure) as well as mouse anti-PD-1 antibody. The tumor-bearing animals were randomized to four groups: no treatment, radiation alone, anti-PD-1 alone, and radiation + anti-PD-1. Survival was followed, and tumor growth was monitored using MRI. Immunohistochemistry, gene expression arrays, and flow cytometry were used to characterize the treatment-induced effects. Pharmacologic inhibitors of T-lymphocytes, bone marrow derived macrophages, and microglia were used to assess the respective roles of different immune populations in observed treatment effects.

Results

We found the combined treatment with high dose radiation and immunotherapy to be highly effective with a 75% complete pathologic response and dramatically improved survival outcomes. We found both CD8+ T-cells and macrophages to be necessary for the full effect of combined therapy, with T lymphocytes appearing to play a role early on and macrophages mediating a later phase of the combined treatment effect. Radiation treatment appeared to trigger macrophage repolarization, increasing M1/M2 ratio.

Conclusions

These findings point to a novel immunologic mechanism underlying the interaction between radiotherapy and immunotherapy. They also provide the basis for clinical investigation of immunogenic dose radiation in combination with immune checkpoint blockade as a potential treatment approach for newly diagnosed high grade gliomas.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Jetzt e.Med zum Sonderpreis bestellen!

Sichern Sie sich jetzt Ihr e.Med-Abo und sparen Sie 50 %!

Weitere Produktempfehlungen anzeigen
Zusatzmaterial
Literatur
Über diesen Artikel
  1. Sie können e.Med Neurologie & Psychiatrie 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

  2. Sie können e.Med Neurologie 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

  3. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.