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REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1566869
Immune Inhibitory Receptor Agonist Therapeutics
Provisionally accepted- NextCure, Inc., Beltsville, United States
The immune system maintains the health of an organism through complex sensing and communication mechanisms. Receptors on the surface of immune cells respond to stimuli resulting in activity described at its most basic as inhibitory or stimulatory. Significant progress in therapeutic intervention has occurred by modulating these pathways, yet much remains to be accomplished. Therapeutics that antagonize, or block, immune inhibitory receptor (IIR) pathways, such as checkpoint inhibitors in cancer are a key example. Antagonism of immune stimulatory receptors (ISRs) for dysregulated inflammation and autoimmunity have received significant attention. An alternative strategy is to agonize, or induce signaling, in immune pathways to treat disease. Agonism of ISRs has been employed with some success in disease settings, but agonist therapeutics of IIRs have great, untapped potential. This review discusses and highlights recent advances in pre-clinical and clinical therapeutics designed to agonize IIR pathways to treat diseases. In addition, an understanding of IIR agonists based on activity at a cellular level as either agonist suppression of stimulatory cells (SuSt), or a new concept, agonist suppression of suppressive cells (SuSu) is proposed.
Keywords: immune, inhibitory, agonist, therapeutic, receptor
Received: 25 Jan 2025; Accepted: 07 Mar 2025.
Copyright: © 2025 Lovewell, Langermann and Flies. 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:
Dallas B. Flies, NextCure, Inc., Beltsville, United States
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.