Increased CD200 expression in post-transplant lymphoproliferative disorders correlates with an increased frequency of FoxP3(+) regulatory T cells

Abstract

CD200 is a membrane protein with immunosuppressive function and is expressed in many hematopoietic neoplasms, including acute myeloid leukemia (AML), plasma cell myeloma (PCM), and B-cell lymphoproliferative disorders, but is mostly negative in diffuse large cell lymphoma (DLBCL). CD200 has been shown to be a poor prognostic marker in AML and PCM; in AML, its immunomodulatory effect was linked to its ability to induce FoxP3(+) regulatory T cells (Tregs). Post-transplant lymphoproliferative disorders (PTLDs) arise in the setting of immune dysregulation, and tumor-infiltrating T cells, including Tregs, have been shown to correlate with outcome in these disorders. Because there is no literature data and CD200 is a potentially useful diagnostic and prognostic marker, we studied the expression of CD200 in a series of 38 PTLDs by immunohistochemistry (ICH), and found that 23.7% PTLDs were CD200(+) and showed strong membrane and cytoplasmic positivity in the neoplastic cells. All CD200(+) monomorphic PTLDs were DLBCLs and the median FoxP3(+) Treg count/hpf was higher in CD200(+) than in CD200(-) PTLDs: 22.6 vs. 0.30 (p < 0.001). These results indicated that almost a quarter of PTLDs in our series are CD200(+) by IHC, and CD200 expression correlates with the frequency of immunosuppressive Tregs. This is novel data and supports a pathophysiologic link between CD200 activity and Tregs. In our series, the 5-year overall survival was shorter in CD200(+) PTLDs, compared to CD200(-) patients, although this difference did not reach statistical significance. In addition, we find a higher proportion of CD200(+) monomorphic PTLD-DLBCLs (31.0%), as compared to de novo DLBCLs (7-8%, as found here and in other studies). This may indicate differential expression of CD200 in B-cell lymphomas arising in the setting of immune dysregulation, and raises the possibility of anti-CD200 immunotherapy for these cases.

Keywords: CD200; Diffuse large B-cell lymphoma; FoxP3; Post-transplant lymphoproliferative disorder; Tregs.