Sunita Garg¹, Andy Yale², Abbe Crawford², Alexandros Chardas²

¹University of Cambridge, Cambridge, United Kingdom. ²Royal Veterinary College, London, United Kingdom

Objectives

Gliomas are aggressive brain tumours in dogs, with limited effective therapies and a poor prognosis. We aimed to determine the presence of CTLA-4 and PD-L1 immune checkpoint proteins in the tumour microenvironment of canine gliomas, as these could represent a valuable target for future immunotherapies.

Methods

Tissue from nine canine gliomas and three normal brains were selected from the Royal Veterinary College’s pathology department and companion animal brain bank. Gliomas were subtyped and graded on routine histopathology. Immunohistochemistry for CTLA-4 and PD-L1 was performed on cases and controls and evaluated qualitatively and semi-quantitatively. To validate the antibodies, we performed IHC and western blot analysis on appropriate positive and negative control tissues.

Results

Most gliomas were high-grade oligodendrogliomas (n = 5 [56%]). No PDL-1 labelling was detected in canine glioma tissue beyond non-significant background staining, nor normal brain parenchyma. CTLA-4 was not detected in canine glioma nor normal brain. Both PD-L1 and CTLA-4 were identified in canine lymphoid tissue. Western blot analysis confirmed PD-L1 antibody specificity, although was unsuccessful in validating CTLA-4.

Statement: Impact/ Clinical Significance

Immunotherapy is becoming an important cancer therapy and, given the limited effective options for canine glioma, there is growing interest in its applicability in this disease. However, the results of this pilot study suggest that immunotherapy, specifically targeting PD-L1 and CTLA-4, may not be successful in the treatment of canine glioma since these proteins were not expressed. However, this requires further exploration in a larger study population and range of glioma grades and subtypes.