The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy

// Anqi Shao 1 and David M. Owens 1 , 2 1 Department of Dermatology, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, New York, NY 10032, USA 2 Department of Pathology and Cell Biology, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, New York, NY 10032, USA Correspondence to: David M. Owens, email: do2112@cumc.columbia.edu Keywords: CD200 receptor; oncoimmunology; immunotherapy; tumor microenvironment; immune checkpoint inhibition Received: January 23, 2023     Accepted: January 24, 2023     Published: February 04, 2023 Copyright: © 2023 Shao and Owens. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT CD200 is an immunoregulatory cell surface ligand with proven pro-tumorigenic credentials via its ability to suppress CD200 receptor (CD200R)-expressing anti-tumor immune function. This definitive role for the CD200-CD200R axis in regulating an immunosuppressive tumor microenvironment has garnered increasing interest in CD200 as a candidate target for immune checkpoint inhibition therapy. However, while the CD200 blocking antibody samalizumab is still in the early stages of clinical testing, alternative mechanisms for the pro-tumorigenic role of CD200 have recently emerged that extend beyond direct suppression of anti-tumor T cell responses and, as such, may not be susceptible to CD200 antibody blockade. Herein, we will summarize the current understanding of CD200 expression and function in the tumor microenvironment as well as alternative strategies for potential neutralization of multiple CD200 mechanisms in human cancers.