IL-10 and ARG-1 Concentrations in Bone Marrow and Peripheral Blood of Metastatic Neuroblastoma Patients Do Not Associate with Clinical Outcome

Abstract

The expression of the immunosuppressive molecules IL-10 and arginase 1 (ARG-1), and of FOXP3 and CD163, as markers of regulatory T cells (Treg) and macrophages, respectively, was evaluated in bone marrow (BM) and peripheral blood (PB) samples collected at diagnosis from patients with metastatic neuroblastoma (NB). IL-10 and ARG-1 plasma concentrations were measured and the association of each parameter with patients' outcome was tested. The percentages of immunosuppressive Treg and type-1 regulatory (Tr1) cells were also determined. In both BM and PB samples, IL-10 mRNA expression was higher in metastatic NB patients than in controls. IL-10 plasma concentration was higher in patients with NB regardless of stage. Neither IL-10 expression nor IL-10 plasma concentration significantly associated with patient survival. In PB samples from metastatic NB patients, ARG-1 and CD163 expression was higher than in controls but their expression did not associate with survival. Moreover, ARG-1 plasma concentration was lower than in controls, and no association with patient outcome was found. Finally, in metastatic NB patients, the percentage of circulating Treg was higher than in controls, whereas that of Tr1 cells was lower. In conclusion, although IL-10 concentration and Treg percentage were increased, their contribution to the natural history of metastatic NB appears uncertain.

CD4+CD25hiCD127− Treg and CD4+CD45R0+CD49b+LAG3+ Tr1 cells in bone marrow and peripheral blood samples from children with neuroblastoma

“…In contrast, the percentage of both Treg and Tr1 cells was significantly lower in NB patients (0.34 § 0.11 and 0.07 § 0.019, respectively) than in healthy children (1.09 § 0.16 and 1 § 0.27, respectively) (p D 0.0056 and p < 0.0001), reflecting the observations in the BM samples. These data, obtained in a larger number of PB samples from NB patients and controls than our previous report, 10 confirmed the lower percentage of PB Tr1 cells and suggested that the higher percentage of PB Treg previously reported was inaccurate due to the small sample size.…”

“…8 Treg cells have been previously characterized in peripheral blood (PB) from very small cohorts of NB patients. [9][10][11] A higher percentage of Treg in NB patients than healthy children was reported by us and Tilak et al, whereas Gowda et al showed that their number was similar in lowand high-risk patients.…”

“…Precisely, an increased numbers of Tr1 cells was shown to associate to tumor progression in colorectal cancer, 17 whereas we showed in a small cohort of NB patients that PB Tr1 cells were present in lower percentage than in healthy children. 10 In this study, we have analyzed the percentage of Treg and Tr1 cells in BM and PB samples collected from NB patients at diagnosis as compared to healthy subjects. Moreover, we analyzed potential associations of this frequency to the most important NB prognostic factors, such as age, stage of disease, and MYCN gene amplification.…”

Neuroblastoma causes alterations of the intestinal microbiome, gut hormones, inflammatory cytokines, and bile acid composition

“…Interestingly, implantation of NB cells was also associated with increased serum levels of the anti‐inflammatory cytokine IL‐10. Increased IL‐10 levels are a typical finding for some types of NB and have been associated with metastatic disease …”

Colony stimulating factor 1 receptor blockade improves the efficacy of chemotherapy against human neuroblastoma in the absence of T lymphocytes

“…27 Finally, anti-NB functions of T lymphocytes may be suppressed by high levels of T regulatory cells in NB patients. 28 …”