Myeloid-derived suppressor cell cytokine secretion as prognostic factor in myelodysplastic syndromes

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a critical immunosuppressive role in the tumour micro-environment. Although biological research on MDSCs has made progress, the relationship between the secretion of cytokines by MDSCs and poor prognosis is not clear, and there are no criteria to measure the functional status of MDSCs. Here, we detected the mRNA expression of IL-10, IL-12, TGF-β and TNF-α in MDSCs and the levels of these cytokines in MDSC culture supernatants of patients with myelodysplastic syndromes, and quantified the functional status of MDSCs by IL-10/IL-12 ratio and TGF-β/TNF-α ratio. We found that the ratio of IL-10/IL-12 and TGF-β/TNF-α was significantly higher in higher-risk MDS than in lower-risk MDS and normal control groups. The TGF-β/TNF-α ratio in MDSCs was positively correlated with the percentage of blast cells and was negatively correlated with the percentage of CD3+CD8+ T lymphocytes. Meanwhile, the TGF-β/TNF-α ratio was higher in patients with a lower absolute neutrophil count. It suggested that MDSCs in higher-risk MDS have a stronger immunosuppressive effect and might be related to poor prognosis. Quantifying the functional status of MDSCs with IL-10/IL-12 and TGF-β/TNF-α ratio might help to evaluate the balance of cellular immunity of MDSCs in MDS.

Myeloid-Derived Suppressor Cells: New Insights into the Pathogenesis and Therapy of MDS

“…Therefore, the S100A9–CD33 axis is an important driver of suppressive cytokine production by MDSCs in MDS BM. In line with these data, it has also been reported that the levels of IL-10 and TGFβ1 produced by Lin − /CD33 + / DR − MDSCs are increased in high-risk MDS patients, implying their possible prognostic value in patients with MDS [ 92 ]. Moreover, MDSCs could be themselves cellular sources of proinflammatory cytokines such as IL-1β [ 84 ], contributing to the inflammatory milieu, a well characterized feature of MDS [ 93 ].…”

Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications

“…Furthermore, MDSCs in MDS patients express a specific pattern of BM-homing chemokine receptors (CXCR4, CX3CR1) which probably contributes to their accumulation in the BM. Furthermore, in addition to their accumulation, the immunosuppressive function of MDSCs was suggested to be increased in higher-risk MDS [ 131 ]. The suppression of CD8 + T lymphocyte function was also shown to be mediated by different mechanisms such as the STA3-ARG1 or TIM3/Gal-9 pathways [ 101 , 129 ].…”

Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies

“…In addition, high-risk MDS-derived MDSCs exhibit higher activated activator of transcription (STAT)3 and C-C chemokine receptor type (CCR)2 expression, whereas STAT3 pathway targeting decreases ARG1 expression in MDSCs and partially revokes reduced expression levels of effector molecules in CD8+ T lymphocytes [155]. Thus, MDSCs may contribute to the BM microenvironment switch to an immunosuppressive environment as the MDS disease progresses [156].…”