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72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

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Cerebral metastases of melanoma express potential targets for immunotherapy with checkpoint inhibitors

Gehirnmetastasen des malignen Melanoms exprimieren potentielle Angriffspunkte für eine Therapie mit Checkpoint-Inhibitoren

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  • Saskia Kuhl - University Hospital Cologne, University of Cologne, Neurosurgery, Köln, Deutschland
  • Isabel Peto-Madew - University Hospital Cologne, University of Cologne, Neurosurgery, Köln, Deutschland
  • Roland Goldbrunner - University Hospital Cologne, University of Cologne, Neurosurgery, Köln, Deutschland
  • presenting/speaker Marco Timmer - University Hospital Cologne, University of Cologne, Neurosurgery, Köln, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocP030

doi: 10.3205/21dgnc318, urn:nbn:de:0183-21dgnc3188

Published: June 4, 2021

© 2021 Kuhl et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Checkpoint inhibitors such as Ipilimumab and Nivolumab have significantly improved survival in patients with inoperable or metastatic melanoma. Many cancers produce proteins that suppress the immunological response, specifically cytotoxic T-cells. Checkpoint inhibitors aim to block the inhibitory pathway these proteins stimulate in T-cells, thereby reactivating the cells ability to fight the tumour. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and programmed death-ligand 1 (PDL1) are current targets used in the treatment of melanoma and thus may present potential targets for the precise treatment of cerebral metastases. The objective is to identify and quantify the listed targets in brain metastases.

Methods: The tumours were acquired via operation and immediately frozen using liquid nitrogen. A total of 16 matched tumour samples, 8 metastatic melanoma tumours and 8 recurrent brain tumours, were selected and the proteins were extracted and separated using SDS-PAGE and transferred to a nitrocellulose membrane for incubation with anti-PD1, -PDL1 and -CTLA4 primary antibodies. Secondary antibodies linked to a peroxidase were used for band detection.

Results: PDL-1 was shown to be expressed in metastases (0,747+/-0,1921) and the recurrent tumour (0,7868+/-0,2038). CTLA4 and PD1 are significantly over-expressed in metastases (0,4499+/-0,1877 and 0,4792+/-0,2584 respectively) and the recurrent tumour (0,4757+/-0,4449 and 0,4599+/-0,2289) versus the control group (0,2484+/-0,17 and 0,1049+/-0,0616).

Conclusion: PD1 and CTLA4 are both over-expressed in malignant melanoma and also in its cerebral metastasis. Furthermore, they may also present a target for immunotherapy in the treatment in metastatic melanoma.