The pro-tumor effect of CD200 expression is not mimicked by agonistic CD200R antibodies

Abstract

Tumor-infiltrating immune cells can impact tumor growth and progression. The inhibitory CD200 receptor (CD200R) suppresses the activation of myeloid cells and lack of this pathway results in a reduction of tumor growth, conversely a tumorigenic effect of CD200R triggering was also described. Here we investigated the role of CD200R activation in syngeneic mouse tumor models. We showed that agonistic CD200R antibody reached tumors, but had no significant impact on tumor growth and minor effect on infiltration of immune myeloid cells. These effects were reproduced using two different anti-CD200R clones. In contrast, we showed that CD200-deficiency did decrease melanoma tumor burden. The presence of either endogenous or tumor-expressed CD200 restored the growth of metastatic melanoma foci. On the basis of these findings, we conclude that blockade of the endogenous ligand CD200 prevented the tumorigenic effect of CD200R-expressing myeloid cells in the tumor microenvironment, whereas agonistic anti-CD200R has no effect on tumor development.

CD200-CD200R Pathway in the Regulation of Tumor Immune Microenvironment and Immunotherapy

“…We found that OX110 treatment significantly inhibited tumor foci formation in the lungs. Consistent with this study, Pilch et al recently showed that co-injection of TLR7 agonist and anti-CD200R antibody reshaped TME and induced anti-tumor myeloid cells in the mouse CT26 colon tumor model (61). Thus, targeting CD200R rather than CD200 should be a feasible approach for human cancer therapy.…”

NK Cell-Based Immune Checkpoint Inhibition

“…The inhibitory CD200-CD200R pathway appears to inhibit the effector functions of T cell in an indirect manner via the regulation of macrophages and DCs. Hence, tumor growth could be inhibited by blockade of CD200-CD200R interaction, lending support to the idea that antagonistic CD200 or CD200R antibodies are an option in cancer treatment (278). Samalizumab (a humanized Anti-CD200 antibody) was well-tolerated and demonstrated changes in CD4positive T cells and CD200-positive B-CLL in a dose-dependent manner as well as inducing a dose-dependent linear increase in serum AUC and modest Th1 cytokine responses (279).…”

Positive predictive value of CD200 positivity in the differential diagnosis of chronic lymphocytic leukemia

“…Based on the title and, where needed, abstract, all studies reporting on the diagnostic use of CD200 in LPD were considered for inclusion. Exclusion criteria included reported results not obtained by FC (i.e., immunohistochemistry, gene expression), (Palumbo et al, ; Pilch et al, ) case reports (Sorigue, Juncà, et al, ), review articles (which were however read and their reference list examined for potentially relevant studies) or reported on CD200 only in (4.1) germinal center‐derived or high‐grade malignancies or in (4.2) typically CD103‐positive LPD, including hairy cell leukemia (HCL), HCL‐variant, and splenic diffuse red pulp lymphoma (Espinet et al, ). Publications not excluded at this point were read in full including, where needed, Supplementary material.…”

“…CD200 is a surface glycoprotein present on the membrane of normal B‐cells and B‐cell precursors, some T‐cells, dendritic cells, and neurons. Binding with its receptor, CD200R, favors immune tolerance (Pilch et al, ). CD200 was first described in 2009 as being uniformly present in chronic lymphocytic leukemia (CLL) but absent in mantle cell lymphoma (MCL) (Palumbo et al, ) and a potential diagnostic role was proposed for this marker by flow cytometry (FC).…”