A new research perspective was published in Oncotarget's Volume 14 on February 4, 2023, entitled, “The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy.” 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. In this new research perspective, researchers Anqi Shao and David M. Owens from Columbia University Irving Medical Center summarized 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. “In the future, unbiased genomic- and proteomic-based approaches may help to clarify these issues by identifying tumor-specific mechanisms of CD200 expression regulation across a variety of human cancers that may be leveraged for broader therapeutic benefit.” DOI: https://doi.org/10.18632/oncotarget.28354 Correspondence to: David M. Owens - do2112@cumc.columbia.edu Keywords: CD200 receptor, oncoimmunology, immunotherapy, tumor microenvironment, immune checkpoint inhibition About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957