CD200 Baseline Serum Levels Predict Prognosis of Chronic Lymphocytic Leukemia

Abstract

Membrane-bound CD200 is overexpressed in chronic lymphocytic leukemia (CLL), and there is some evidence that its soluble ectodomain (sCD200) could also be involved in the pathophysiology and the disease. However, very little is known about sCD200’s prognostic significance. sCD200 was tested at diagnosis in 272 patients with CLL and in 78 age- and sex-matched healthy subjects using a specific human CD200 (OX-2 membrane glycoprotein) ELISA kit. A significantly higher concentration of sCD200 was found in CLL patients compared to controls. In our cohort, sCD200 was significantly higher in patients who were older than 66 years, with Binet stage C, unmutated IgVH and unfavorable (del11q or del17p) FISH. Time-to-first treatment and overall survival were significantly shorter in patients with higher sCD200 concentration, using as a cut-off 1281 pg/mL, the median value for sCD200 concentration in the whole CLL cohort. However, the prognostic impact of sCD200 was not confirmed in multivariate analysis. Baseline sCD200 values appeared to have an impact on the response to chemotherapy or chemo-immunotherapy, but not to targeted agents. Collectively, our data show that sCD200 serum levels correlate with more aggressive clinical and biological features and are able to predict a worse prognosis. This work supports the relevant role of CD200 not only as a diagnostic tool but also as a prognostic indicator and a potential therapeutic target in CLL.

CD200 is overexpressed in the pancreatic tumor microenvironment and predictive of overall survival

“…CD200 can be cleaved and expressed as sCD200 in the plasma in patients with CLL [ 38 ]; however, this has not been explored in PDAC. Thus, we investigated whether sCD200 levels were elevated in metastatic PDAC.…”

“…The ectodomain of CD200 has been reported to be shed, and the resulting sCD200 has been reported in the plasma of patients with various types of cancers, including CLL and breast cancer [ 38 , 56 ]. This is the first report to show that sCD200 is expressed in the plasma of PDAC patients.…”

“…Importantly, the CD200 ectodomain is still functional and thus can still interact with its receptor and initiate an immunosuppressive response [ 37 ]. Furthermore, in chronic lymphocytic leukemia (CLL), patients with higher sCD200 levels have worse overall survival (OS) and progression-free survival (PFS) than patients with lower sCD200 [ 38 ]. In PDAC, it is unknown if sCD200 is detectable in the plasma, which MMPs are involved, and if circulating levels of sCD200 correlate with worse OS and PFS in patients.…”

Checkpoint Inhibitors in Dogs: Are We There Yet?

“…Notably, CD200 is frequently expressed in people with chronic lymphocytic leukaemia (CLL) and serves as a diagnostic marker. Elevated serum levels of CD200 have been correlated with poorer prognostic outcomes in CLL patients [ 54 ]. Furthermore, investigations have demonstrated promising outcomes of anti-CD200 therapy in the treatment of gliomas in dogs and also hold potential as a treatment modality for CLL in dogs [ 55 ].…”

Cancel cancer: The immunotherapeutic potential of CD200/CD200R blockade

“…High levels of CD200 have been found to be expressed on various types of human cancer cells, including hairy cell leukemia ( 55 ), acute myeloid leukemia ( 56 ), malignant melanoma ( 22 ), CLL ( 21 ), multiple myeloma ( 21 ), testicular cancer ( 21 ), renal carcinoma ( 21 ), colon carcinoma ( 21 ), and GBM ( 57 ). Moreover, CD200 overexpression is correlated with poor prognosis among some of these cancers, suggesting that high levels of CD200 may facilitate tumorigenesis ( 21 , 58 – 60 ). This observation can be explained by CD200’s primarily inhibitory role in the tumor microenvironment (TME) and the mechanisms through which the protein suppresses immune cell function and activation.…”