Page 214 - 2021_09-Haematologica-web

Letters to the Editor
Prognostic impact of soluble CD163 in patients with diffuse large B-cell lymphoma
We assessed the clinical utility of soluble CD163 (sCD163) in patients with diffuse large B-cell lymphoma (DLBCL), by measuring sCD163 levels prior to, during and after treatment in two independent cohorts. Our results demonstrate that pre-treatment sCD163 levels decrease in response to therapy and, if elevated, predict an unfavorable outcome. The findings suggest that sCD163 represents a useful and easily assessable bio- marker for therapeutic monitoring in DLBCL.
Although the combination of rituximab with chemotherapy has revolutionized treatment in DLBCL,1 approximately 20-30% of patients relapse with a dismal survival.2 International Prognostic Index-based classifica- tions are used to predict outcomes,3 but the composition of the tumor microenvironment has also been recognized to have prognostic impact on survival.4 Macrophages infiltrating into the tumor microenvironment are usually polarized as tumor-associated macrophages (TAM), which strongly express CD163,5 and CD163 expression in the tumor microenvironment is regarded as a marker of TAM. Elevated levels of CD163 ectodomain, a sCD163, have been detected in serum, and associated with adverse outcome in lymphoid malignancies.6,7 While TAM content predicts survival in DLBCL4,8 the clinical relevance of sCD163 is unknown.
We examined the clinical utility of sCD163 in two independent cohorts of patients with DLBCL to gain fur-
ther understanding of the biological role of macrophages during the clinical course of DLBCL. A prospective clini- cal trial cohort and a population-based cohort were used to reach generalizable results.
The trial cohort included patients <65 years with high- risk DLBCL treated with dose-dense immunochemother- apy in the Nordic NLG-LBC-05 phase II trial.9 Available samples included 119 pre-treatment and 94 paired mid- treatment samples. Samples from five healthy volunteers formed a control group. The trial was registered at www.ClinicalTrials.gov as NCT01325194. All patients gave written informed consent to the study. The Institutional Review Boards, National Medical Agencies, and Ethics Committees in Finland, Norway, Denmark, and Sweden approved the protocol and sampling.
The population-based cohort was obtained from the Swedish biobank U-CAN10 and included 125 pre-treat- ment samples collected between 2010 and 2016. Available paired samples included 30 mid-treatment sam- ples, 71 post-treatment samples from patients in com- plete remission, and 11 samples taken during primary progressive or relapsing disease. A majority of the patients (93%) were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP)-based therapy. Complete remission was defined in clinical routine. All patients gave written informed biobank consent. The study was approved by the Regional Board of the Ethical Committee in Uppsala, Sweden.
In the trial cohort, sCD163 was measured using a Quantikine enzyme-linked immunosorbent assay
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Figure 1. sCD163 levels in two cohorts and correlation between pre-treatment sCD163 levels, CD163+ tumor-associated macrophages and CD163 mRNA levels in the trial cohort. (A) Comparison of sCD163 levels in pre-treatment and mid-treatment samples (after three courses) in the trial cohort, and in healthy volunteers. (B) sCD163 levels in pre-treatment samples compared to those in paired mid-treatment sam- ples and paired post-treatment samples from patients in complete remission, and at primary progressive or relapsing disease in the popu- lation-based cohort. For graphical reasons the two extreme outliers with pre-treatment sCD163 levels over 11,000 ng/mL are not shown in the figure, but are included in the statistical analyses. (C) Correlation of pre-treatment sCD163 levels and CD163+ tumor-associated macrophages (TAM) in the tumor tissue in the trial cohort. (D) Correlation of pre-treatment sCD163 levels and CD163 gene expression levels from the matching tumor tissue in the trial cohort.
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haematologica | 2021; 106(9)