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

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.

CD30 Expression in Monomorphic Posttransplant Lymphoproliferative Disorder, Diffuse Large B-Cell Lymphoma Correlates With Greater Regulatory T-Cell Infiltration.

OBJECTIVES: CD30 is a protein thought to promote cell proliferation/survival and downregulate the immune response. Twenty percent to 40% of de novo diffuse large B-cell lymphomas (DLBCLs) express CD30, and some patients have been treated with the anti-CD30 agent brentuximab. In the solid organ transplant setting, allograft regulatory T cells (Tregs) have been shown to be modulated via CD30 signaling. METHODS: Posttransplant lymphoproliferative disorders (PTLDs) constitute a heterogeneous group of lymphomas, and since CD30 expression has been rarely formally assessed in PTLDs, we analyzed a cohort of PTLDs. RESULTS: We found that 26 (79%) of 33 PTLDs were CD30+. Of these, 17 (77%) of 22 DLBCL monomorphic PTLDs were CD30+ compared with 56 (38%) of 148 de novo DLBCLs (P = .009). The median FoxP3+ Treg count was higher in CD30+ than in CD30- PTLDs, 3.0 vs 0 (P = .012). CONCLUSIONS: These findings suggest a pathophysiologic link between CD30 activity and Tregs and may indicate differential expression of CD30 in B-cell lymphomas arising in the setting of immune dysregulation.