Serum CD163 and TARC as Disease Response Biomarkers in Classical Hodgkin Lymphoma

Abstract

Purpose: Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, whereas benign CD163 þ M2 tissue-associated macrophages (TAM) are prominent. CD163 þ cells within the malignant node may be prognostic, but there is no data on serum CD163 (sCD163). The HRS-specific serum protein sTARC shows promise as a disease response biomarker. Tumor-specific and tumor-infiltrating circulating biomarkers have not been compared previously. Experimental Design: We prospectively measured sCD163 and sTARC in 221 samples from 47 patients with Hodgkin lymphoma and 21 healthy participants. Blood was taken at five fixed time-points prior, during, and after first-line therapy. Results were compared with radiological assessment and plasma Epstein-Barr virus DNA (EBV-DNA). Potential sources of circulating CD163 were investigated, along with immunosuppressive properties of CD163.Results: Pretherapy, both sCD163 and sTARC were markedly elevated compared with healthy and complete remission samples. sCD163 better reflected tumor burden during therapy, whereas sTARC had greater value upon completion of therapy. sCD163 correlated with plasma EBV-DNA, and associated with B symptoms, stage, and lymphopenia. Circulating CD163 þ monocytes were elevated in patients, indicating that sCD163 are likely derived from circulating and intratumoral cells. Depletion of cHL CD163 þ monocytes markedly enhanced T-cell proliferation, implicating monocytes and/or TAMs as potential novel targets for immunotherapeutic manipulation. Conclusion:The combination of circulating tumor-infiltrate (sCD163) and tumor-specific (sTARC) proteins is more informative than either marker alone as disease response biomarkers in early and advanced disease during first-line therapy for cHL.

The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases

“…18 As a prognostic marker in EBV 1 hematologic malignancies, cell-free EBV DNA has been shown to be associated with survival outcomes in HL and extranodal natural killer/T-cell lymphoma (ENKTL), as well as complement or correlate with other blood-based prognostic markers, such as serum survivin in ENKTL and soluble CD163 in HL. [19][20][21][22][23] Across a range of lymphomas, there is mounting evidence that the serial assessment of cellfree EBV DNA copy number can inform the dynamics of EBV 1 disease status during and following therapy. 24 Despite the growing interest in cell-free EBV DNA as a tumor marker, few studies have addressed the significance of detecting EBV DNA in hospitalized patients.…”

Plasma MicroRNA Are Disease Response Biomarkers in Classical Hodgkin Lymphoma

“…Furthermore, it is impractical to perform PET/CT before each follow-up visit. New approaches such as blood biomarkers might assist interpretation of conventional measures of disease response to better identify those that could be spared excessive treatment and those in which change in therapy should be expedited (5,6). Circulating disease response biomarkers have the added advantage of being noninvasive and practical for frequent testing.…”

“…Gene expression profiling of the diseased node in cHL has recently been shown to predict overall survival (17). We recently demonstrated that circulating cell-free biomarkers of both tumor-infiltrating cells (CD163) and HRS cells [TARC and Epstein-Barr virus (EBV)-DNA] reflect disease response in cHL, but that relative to each other, HRS and tumor-infiltrate-associated protein biomarkers had distinct kinetics following initiation of therapy (5).…”

Serum CYFRA21-1 as an effective tumor biomarker for patients with nasopharyngeal carcinoma

“…However, due to limitations, EBV-related protein was not a useful biomarker for NPC. Ideal biomarkers must be specific, sensitive and easy to assay and interpret, and they must have high reproducibility and comparability between different laboratories [11].…”