Circulating levels and clinical significance of soluble CD40 in patients with hematologic malignancies

Abstract

BACKGROUNDCD40 plays a critical role in immunoregulation, and CD40 ligation is being investigated as a therapy for hematologic malignancies. Although soluble CD40 (sCD40) is a potential modulator of both antitumor responses and CD40‐based therapies, the levels and significance of sCD40 in patients with hematologic malignancies are unknown.METHODSThe authors evaluated serum/plasma sCD40 levels using an enzyme‐linked immunoassay in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and multiple myeloma (MM).RESULTSLevels of sCD40 were elevated in serum (>1.697 ng/mL) or plasma (>0.649 ng/mL) from 73% of patients with CLL, 80% of patients with MCL, 40% of patients with AML, 43% of patients with MDS, and 33% of patients with MM. Multivariate analysis of patients with MM demonstrated that elevated sCD40 was a significant, independent predictor of poor survival. In multivariate analysis of patients with AML, sCD40 was a significant prognostic factor when the interaction of age and sCD40 was included as a variable. Further analysis demonstrated that elevated sCD86 levels were associated with significantly shorter survival only in AML patients younger than age 64 years. Release of sCD40 by CLL cells was induced by cross‐linking with CD40 monoclonal antibody.CONCLUSIONSMany patients with hematologic malignancies have elevated circulating levels of sCD40, and these elevated levels are associated with a poor prognosis at least in patients with MM and AML, suggesting that sCD40 may have a role in modulating antitumor responses and also may be a useful prognostic marker. In addition, the findings suggested that further studies will be required to determine the effect of circulating sCD40 on the clinical effectiveness of CD40‐ligating reagents used in the treatment of hematologic malignancies. Cancer 2006. © 2006 American Cancer Society.

A functional TNFRSF5 gene variant is associated with risk of lymphoma

“…Regarding T-cell and dendritic cell interactions, deviations in sCD40 levels may impact tumor-specific immune responses. In contrast to earlier studies that reported elevated circulating sCD40 levels in persons with arthritis, renal failure, lung cancer, 10,38,39 and hematologic malignancies, 40 our results showed that sCD40 levels were higher in healthy controls than in DLBCL and FL cases. The relevance of sCD40 in lymphomagenesis will need further investigation.…”

Imbalance in serum soluble CD30/CD30L and CD40/CD40L systems are associated with ovarian tumors

“…Some interesting information was also delivered by Caggiari et al [28], who results showed significantly higher concentration of the cytokine. Hock et al [29] evaluated serum and plasma levels of CD40 in patients with hematological diseases, among other chronic lymphocytic leukemia or the mantle cell lymphoma.…”

Soluble CD22 as a tumor marker for hairy cell leukemia

“…A wide variety of soluble receptors and antigens have been reported associated with malignancies, including soluble granulocyte-monocyte colony-stimulating factor receptor in acute myelogenous leukemia (AML), 1 soluble CD20 in non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and Hodgkin disease (HD), 2,3 soluble CD25 (soluble interleukin-2 receptor alpha or sTac) in CD25 ϩ T-and B-cell malignancies, solid tumors and in autoimmune disorders, [4][5][6] soluble CD27 in indolent NHL, 7 soluble CD30 in autoimmune disorders 8 and in HD, 9,10 soluble CD40 in multiple myeloma (MM), CLL, mantle cell lymphoma (MCL), and AML, 11 soluble CD44 in NHL and early CLL, 12 soluble CD52 in CLL, 13 soluble CD80 in CLL and MCL, 14 soluble CD86 in MM and NHL, 15,16 soluble CD137 in leukemias and lymphomas, 3,17 soluble CD138 in MM 18 and CLL, 19 soluble CD307 (IRTA2, FcRH5) in hairy cell leukemia (HCL), MM, CLL, and MCL, 20,21 beta 2 -microglobulin in HD, MM, and solid tumors, [22][23][24] soluble tumor necrosis factor receptor in NHL, 25 and soluble mesothelin in mesotheliomas. 26 However, none of these markers is routinely used in the management of patients with B-cell malignancies.…”