Molecular profiling of an osseous metastasis in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape

Acta Neuropathologica Communications
Malte MohmeManfred Westphal

Abstract

Peripheral metastases of glioblastoma (GBM) are very rare despite the ability of GBM cells to pass through the blood-brain barrier and be disseminated through the peripheral blood. Here, we describe a detailed genetic and immunological characterization of a GBM metastasis in the skeleton, which occurred during anti-PD-1 immune checkpoint therapy. We performed whole genome sequencing (WGS) and 850 K methylation profiling of the primary and recurrent intracranial GBM as well as one of the bone metastases. Copy number alterations (CNA) and mutational profiles were compared to known genomic alterations in the TCGA data base. In addition, immunophenotyping of the peripheral blood was performed. The patient who was primarily diagnosed with IDH-wildtype GBM. After the resection of the first recurrence, progressive intracranial re-growth was again detected, and chemotherapy was replaced by PD-1 checkpoint inhibition, which led to a complete intracranial remission. Two months later MR-imaging revealed multiple osseous lesions. Biopsy confirmed the GBM origin of the skeleton metastases. Immunophenotyping reflected the effective activation of a peripheral T-cell response, with, however, increase of regulatory T cells during disease progre...Continue Reading

References

Oct 29, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ryo UedaHideho Okada
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Oct 4, 2011·Journal of Neuro-oncology·Gauri KalokheJeffrey J Raizer
Nov 2, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ekokobe FonkemEric T Wong
Feb 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jacky T YeungHideho Okada
Oct 26, 2013·Journal of Molecular Neuroscience : MN·Lijun SunDefu Chen
Feb 26, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jackson D HamiltonChristiane Matuschek
Mar 7, 2014·Journal of Cancer Research and Clinical Oncology·Sopiko JimsheleishviliRicardo J Komotar
Aug 1, 2014·Science Translational Medicine·Carolin MüllerSabine Riethdorf
Aug 21, 2014·Cancer Discovery·James P SullivanDaniel A Haber
Jul 3, 2015·Oncoimmunology·Lionel ApetohAna C Anderson
Sep 16, 2015·Nature Biotechnology·Sachet A ShuklaGad Getz
Dec 26, 2015·World Neurosurgery·C Rory GoodwinDaniel M Sciubba
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Jun 9, 2016·Nature Genetics·Jiguang WangRaul Rabadan
Jul 23, 2016·Journal of Neurosurgery·Robert C RennertClark C Chen
Nov 3, 2016·Nature Reviews. Clinical Oncology·Malte MohmeKlaus Pantel
Dec 3, 2016·Nucleic Acids Research·Simon A ForbesPeter J Campbell
Mar 28, 2017·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Haydn A HoffmanDaniel C Lu
Jan 20, 2018·Drugs·Kristen K Ciombor, Richard M Goldberg
Feb 16, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Malte MohmeKatrin Lamszus
Mar 15, 2018·Nature·David CapperStefan M Pfister
Apr 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Chih-Ping MaoT-C Wu
Apr 11, 2018·Cancer Cell·Roberta ZappasodiJedd D Wolchok
Jul 18, 2018·Nature Methods·Sangtae KimChristopher T Saunders
Aug 2, 2018·British Journal of Cancer·Ilona KrolNicola Aceto
Aug 15, 2018·Nature Medicine·Pakawat ChongsathidkietPeter E Fecci
Jan 16, 2019·Nature Genetics·Robert M SamsteinLuc G T Morris
Apr 18, 2019·Revista da Associação Médica Brasileira·Marcelo Lemos Vieira da Cunha, Marcos Vinicius Calfat Maldaun
Jul 6, 2019·Frontiers in Immunology·Andrea BaloghNandor Gabor Than
Sep 5, 2019·Breast Cancer Research : BCR·Carlotta RiebensahmHarriet Wikman
Sep 14, 2019·Radiology Case Reports·Jeroen SwinnenSofie Van Cauter
Jan 22, 2020·BMC Cancer·Melissa UmphlettRaymund L Yong

❮ Previous
Next ❯

Citations

May 28, 2021·Arkhiv patologii·M V RyzhovaN K Serova
Jun 1, 2021·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Sana MohiuddinSoumen Khatua

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
methylation profiling
flow-cytometry
exome sequencing
light microscopy

Software Mentioned

OncoPrint
Ensembl Variant Predictor ( VEP )
FACSDiva
- FREEC
GnomAD
R Foundation R
Fiji
GraphPad Prism
Adobe Illustrator CC
Control

Related Concepts

Related Feeds

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Related Papers

Zhonghua wai ke za zhi [Chinese journal of surgery]
H H Jiang, S Lin
Epigenetics : Official Journal of the DNA Methylation Society
Jennifer ClarkeNagi G Ayad
© 2021 Meta ULC. All rights reserved