Tumor-Associated Macrophage (TAM)-Related Cytokines, sCD163, CCL2, and CCL4, as Novel Biomarkers for Overall Survival and Time to Treatment in Waldenstrom's Macroglobulinemia: Emphasis on Asymptomatic WM.

Waldenstrom's Macroglobulinemia (WM) is a heterogeneous disease, and the majority of patients tend to have a long course. Nevertheless, it is imperative to detect patients who have a high risk of progression and who benefit from closer follow-up. Many recent studies have displayed the CD163-positive tumor-associated macrophages (TAMs) contribution in the pathogenesis of various hematological neoplasms and solid tumors. Soluble CD163 (sCD163) can be measured in serum, along with other TAM-chemoattractant cytokines, such as CCL2 and CCL4, and their levels are used to determine macrophage activation. In the current study, we investigated the correlation between sCD163, CCL2, and CCL4, with parameters of WM progression and survival. Out of a total of 204 WM patients, serum sCD163, CCL2, and CCL4 were measured in 75, 64, and 65 patients' frozen sera at diagnosis, along with 30 healthy individuals (HIs) using an enzyme-linked immunosorbent assay (ELISA). We achieved to demonstrate that shorter Time to Treatment (TTT) was observed in 2 years and 7 years intervals in all patients with a ratio of CD163/CCL4 above median (p = 0.003 and p = 0.024, respectively) and decreased TTT was observed in all asymptomatic WM (AWM) patients with values of CCL4 above the median (p = 0.018). Moreover, significantly decreased overall survival (OS) (p = 0.033) was observed in all WM patients with CCL2 values above the median. Our results indicate that sCD163, CCL2, and CCL4 could be utilized as prognostic markers in WM.