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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1544949
This article is part of the Research Topic New Insights in Veterinary Cancer Immunology Volume II View all articles
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Immunotherapy using immune checkpoint inhibitors (ICIs) represents a promising therapeutic approach for canine cancer patients. Similar to human cancer patients, the concurrent use of corticosteroids may attenuate the efficacy of immune checkpoint inhibitors in dogs. In this study, we evaluated the impact of corticosteroid therapy on canine peripheral blood mononuclear cell (cPBMC) composition and the in vitro response to PD-1/PD-L1 axis blockade and recombinant human IL-12 (rhIL-12) stimulation. cPBMC samples were collected from 24 healthy, 44 cancer-bearing untreated, and 33 cancer-bearing corticosteroid pre-treated dogs. Lymphocytes were polyclonally stimulated with Staphylococcus Enterotoxin B (SEB) and either atezolizumab, a cross-functional anti-PD-L1 ICI, or recombinant human IL-12 (rhIL-12). We analyzed the absolute and relative changes in canine interferon-gamma (cIFNɣ) production. Stimulation with gilvetmab, a recently developed canine anti-PD-1 ICI, revealed comparable results to atezolizumab. Moreover, we assessed the influence of corticosteroid pre-treatment on cPBMC composition by flow cytometry. Corticosteroid treatment significantly affected the immune profile, primarily the monocytic compartment, and functional cIFNɣ response of cPBMCs. Nevertheless, responses to immunotherapy appeared to be highly individual. Overall, we observed trends suggesting that prior corticosteroid therapy may compromise the efficacy of PD-1/PD-L1 axis blockade and IL-12 in dogs with cancer. While the dose and timing of corticosteroid administration in this study reflected clinical reality and would not justify withholding this emerging therapeutic option, steroid pretreatment may be a confounder for PD-1/PD-L1 axis blockade or IL-12 therapy in canine oncology.
Keywords: Immunotherapy, Immune checkpoint inhibitor, Cancer, atezolizumab, Gilvetmab, corticosteroid, rhIL-12
Received: 13 Dec 2024; Accepted: 24 Mar 2025.
Copyright: © 2025 Zimmermann, Taskoparan, Fuchs, Pantelyushin, Maheswaran, Schnyder, Hartnack, Carla and vom Berg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Johannes vom Berg, University of Zurich, Zürich, Switzerland
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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