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Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro
Craig-Meyer, D. Hollenbaugh, J.A. Morgado, S. McGee, K. Perkins, Ethan Yarzabek, B. Lapinski, P. Rowse, A. Cooper, C. Fortunato, M.
Craig-Meyer, D.
Hollenbaugh, J.A.
Morgado, S.
McGee, K.
Perkins, Ethan
Yarzabek, B.
Lapinski, P.
Rowse, A.
Cooper, C.
Fortunato, M.
Publication Date
2025-02
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© 2025 Labcorp. Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the
posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
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2025-01-29
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Perkins_et_al_2025.pdf
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Abstract
Immunotherapeutics targeting immune checkpoint receptors or their ligands (i.e., immune checkpoint inhibitors), have been groundbreaking in the field of oncology, radically changing the approach to treatment and improving the clinical outcomes of an ever-expanding list of solid tumors and hematological malignancies. However, immune checkpoint inhibitors (ICI) are not devoid of side effects, collectively regarded as immune-related adverse events (irAE); they are not easily uncovered in preclinical immunotoxicological investigations and are often due to the very low expression of their targets in immunologically-unchallenged non-clinical species. We have characterized expression of a broad range of immune checkpoint receptors in peripheral blood mononuclear cell (PBMC) subpopulations from cynomolgus monkeys and healthy human volunteers, under resting and T-cell stimulatory conditions by multicolor flow cytometry to inform appropriate species selection for modeling potential irAE in immunotherapeutic preclinical research. Focusing on the response of the main lymphocyte populations to interleukin (IL)-2 alone, or in combination with anti-CD3 and anti-CD28 antibodies, checkpoints with shared similarities and key differences between the two species were identified. The results of this first study provide a database for the expression and response to stimulation for immune checkpoint receptors and can help guide future model selection in the design of preclinical studies involving immunotherapeutics directed against these targets.
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Craig-Meyer D, Hollenbaugh JA, Morgado S et al (2025) Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro. Journal of Immunotoxicology. 22(1): 2462106.
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