CD200R signaling in tumor tolerance and inflammation: A tricky balance

The inhibitory CD200–CD200 receptor (CD200R) interaction is essential to prevent massive inflammatory responses and immune pathology during microbial infection. Since CD200 expression on human malignancies is associated with tumor progression, CD200 blocking antibodies are currently tested in clinical trials to boost anti-tumor responses. Here we discuss that CD200-mediated suppression of anti-tumor responses may not only be mediated by the tumor itself, but also by CD200 expressed on healthy tissue. However, in cancers that benefit from inflammation, the blockade of CD200 could result in enhanced tumor growth. We conclude that CD200 blockade forms a potential therapeutic option to strengthen anti-tumor responses which is not restricted to treatment of CD200 expressing tumors.

Model depicting the possible dual effect of CD200R signaling on tumor outgrowth. CD200R-regulated inflammation can enhance immune anti-tumor responses but also stimulate tumor-promoting inflammation. Solid arrows indicate stimulation, blunt arrows indicate inhibition.Figure optionsDownload high-quality image (88 K)Download as PowerPoint slideHighlights
► CD200R signaling orchestrates the strength of the immune response in microbial infection.
► CD200 expression on tumors positively affects their outgrowth.
► CD200R signaling not only has a local but also a systemic regulatory effect on tolerance.
► Blockade of CD200R-signaling may stimulate pro-tumorigenic inflammation.