Prior corticosteroid treatment alters cPBMC composition and IFNγ response to immunotherapy in canine cancer
BackgroundImmunotherapy 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 eval...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544949/full |
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| author | Anna Barbara Emilia Zimmermann Anna Barbara Emilia Zimmermann Betül Taskoparan Daniel Fuchs Daniel Fuchs Stanislav Pantelyushin Mathischan Maheswaran Manuela Schnyder Sonja Hartnack Carla Rohrer Bley Johannes vom Berg |
| author_facet | Anna Barbara Emilia Zimmermann Anna Barbara Emilia Zimmermann Betül Taskoparan Daniel Fuchs Daniel Fuchs Stanislav Pantelyushin Mathischan Maheswaran Manuela Schnyder Sonja Hartnack Carla Rohrer Bley Johannes vom Berg |
| author_sort | Anna Barbara Emilia Zimmermann |
| collection | DOAJ |
| description | BackgroundImmunotherapy 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 Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) axis blockade and recombinant human Interleukin-12 (rhIL-12) stimulation. MethodscPBMC samples were collected from 24 healthy, 44 cancer-bearing untreated, and 33 cancer-bearing corticosteroid pre-treated dogs. Lymphocytes were polyclonally stimulated with Staphylococcal Enterotoxin B (SEB) and either atezolizumab, a cross-functional anti-PD-L1 ICI, or 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. ResultsCorticosteroid 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. ConclusionsOverall, 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, corticosteroid pretreatment may be a confounder for PD-1/PD-L1 axis blockade or IL-12 therapy in canine oncology. |
| format | Article |
| id | doaj-art-7f7663ba81e943c7838ea6603f267868 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-7f7663ba81e943c7838ea6603f2678682025-08-20T02:12:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15449491544949Prior corticosteroid treatment alters cPBMC composition and IFNγ response to immunotherapy in canine cancerAnna Barbara Emilia Zimmermann0Anna Barbara Emilia Zimmermann1Betül Taskoparan2Daniel Fuchs3Daniel Fuchs4Stanislav Pantelyushin5Mathischan Maheswaran6Manuela Schnyder7Sonja Hartnack8Carla Rohrer Bley9Johannes vom Berg10Clinic for Radiation Oncology and Medical Oncology, University Animal Hospital, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Laboratory Animal Science, Vetsuisse Faculty, University of Zurich, Schlieren, SwitzerlandInstitute of Laboratory Animal Science, Vetsuisse Faculty, University of Zurich, Schlieren, SwitzerlandClinic for Radiation Oncology and Medical Oncology, University Animal Hospital, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Laboratory Animal Science, Vetsuisse Faculty, University of Zurich, Schlieren, SwitzerlandInstitute of Laboratory Animal Science, Vetsuisse Faculty, University of Zurich, Schlieren, SwitzerlandInstitute of Parasitology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandSection of Epidemiology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandClinic for Radiation Oncology and Medical Oncology, University Animal Hospital, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Laboratory Animal Science, Vetsuisse Faculty, University of Zurich, Schlieren, SwitzerlandBackgroundImmunotherapy 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 Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) axis blockade and recombinant human Interleukin-12 (rhIL-12) stimulation. MethodscPBMC samples were collected from 24 healthy, 44 cancer-bearing untreated, and 33 cancer-bearing corticosteroid pre-treated dogs. Lymphocytes were polyclonally stimulated with Staphylococcal Enterotoxin B (SEB) and either atezolizumab, a cross-functional anti-PD-L1 ICI, or 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. ResultsCorticosteroid 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. ConclusionsOverall, 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, corticosteroid pretreatment may be a confounder for PD-1/PD-L1 axis blockade or IL-12 therapy in canine oncology.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544949/fullimmunotherapyimmune checkpoint inhibitorcanceratezolizumabgilvetmabcorticosteroid |
| spellingShingle | Anna Barbara Emilia Zimmermann Anna Barbara Emilia Zimmermann Betül Taskoparan Daniel Fuchs Daniel Fuchs Stanislav Pantelyushin Mathischan Maheswaran Manuela Schnyder Sonja Hartnack Carla Rohrer Bley Johannes vom Berg Prior corticosteroid treatment alters cPBMC composition and IFNγ response to immunotherapy in canine cancer Frontiers in Immunology immunotherapy immune checkpoint inhibitor cancer atezolizumab gilvetmab corticosteroid |
| title | Prior corticosteroid treatment alters cPBMC composition and IFNγ response to immunotherapy in canine cancer |
| title_full | Prior corticosteroid treatment alters cPBMC composition and IFNγ response to immunotherapy in canine cancer |
| title_fullStr | Prior corticosteroid treatment alters cPBMC composition and IFNγ response to immunotherapy in canine cancer |
| title_full_unstemmed | Prior corticosteroid treatment alters cPBMC composition and IFNγ response to immunotherapy in canine cancer |
| title_short | Prior corticosteroid treatment alters cPBMC composition and IFNγ response to immunotherapy in canine cancer |
| title_sort | prior corticosteroid treatment alters cpbmc composition and ifnγ response to immunotherapy in canine cancer |
| topic | immunotherapy immune checkpoint inhibitor cancer atezolizumab gilvetmab corticosteroid |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544949/full |
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