Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of bone marrow cells originating from immature myeloid cells. They exert potent immunosuppressive activity and are closely associated with the development of various diseases such as malignancies, infections, and inflammation. In malignant tumors, MDSCs, one of the most dominant cellular components comprising the tumor microenvironment, play a crucial role in tumor growth, drug resistance, recurrence, and immune escape. Although the role of MDSCs in solid tumors is currently being extensively studied, little is known about their role in hematologic malignancies. In this review, we comprehensively summarized and reviewed the different roles of MDSCs in hematologic malignancies and hematopoietic stem cell transplantation, and finally discussed current targeted therapeutic strategies.Affiliation: Kindly check and confirm the processed affiliations are correct. Amend if any.correct

The study aims to investigate the effects of the alcohol extract of Coreopsis tinctoria Nutt (AC) on diabetic nephropathy (DN) mice. A total of 30 db/db (DN) mice were divided into 3 groups, which were treated with AC (300 mg/kg/day), metformin (180 mg/kg/day), or saline by gavage for 10 weeks. Ten db/m mice treated with saline were used as normal control (NC group). Body weight (BW) and fasting blood glucose (FBG), HbA1c, 24 h urinary albumin excretion (UAE), and renal pathological fibrosis were analyzed. Expression of miR-192, miR-200b, and proteins in the PTEN/PI3K/AKT pathway was analyzed by qPCR or western blot. The DN mice had significantly higher BW, FBG, and 24 h UAE, as well as more severe pathological fibrosis when compared with NC. Treatment of AC could decrease BW, FBG, and 24 h UAE and alleviated kidney damage. Compared with the NC group, expressions of miR-192 and miR-200b were increased, whereas their target proteins (ZEB2 and PTEN) were reduced in the kidneys of DN mice, which further modulated the expression of their downstream proteins PI3K p85α, P-AKT, P-smad3, and COL4 α1; these proteins were increased in the kidneys of DN mice. In contrast, AC treatment reversed the expression changes of these proteins. These findings demonstrate that AC may protect the kidneys of DN mice by decreasing miR-192 and miR-200b, which could further regulate their target gene expression and modulate the activity of the PTEN/PI3K/AKT pathway to reduce the degree of renal fibrosis.

Background and AimMany studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS.MethodsA full-scale search strategy was used to search relevant published studies in PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library until January 2020 using a random-effects model and the pooled risk ratio (RR) with 95% confidence interval as the effect indicator. Statistical analyses were performed using RevMan 5.3.ResultsThis meta-analysis included eight studies comprising 1047 patients. A lower RR of overall response rate (ORR) (RR: 0.65; 95% CI, 0.47–0.9) and grade ≥3 bleeding events (RR: 0.36; 95% CI, 0.36–0.92) were observed after romiplostim and eltrombopag treatment compared with placebo. The pooled RR for the ORR and grade ≥3 bleeding events were 0.58 (95% CI: 0.41–0.83, P = 0.003) and 0.6 (95% CI: 0.37–0.96, P = 0.03) in eltrombopag, respectively. A lower ORR in intermediate- or high-risk MDS (RR: 0.63; 95% CI: 0.45–0.88, P = 0.006) was observed. No difference in mortality, serious adverse events, platelet transfusion, hematologic improvement, and AML transformation was observed.ConclusionsThrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag were effective in reducing bleeding events, especially grade ≥3 bleeding events. However, it might reduce the ORR of MDS, especially in eltrombopag treatment group or high-risk MDS group. Due to the limited treatment of MDS and the poor response to the drug, this may be a selection method for MDS combined with fatal bleeding, although further research is needed to confirm the effectiveness of this approach.

Myeloid-derived suppressor cells (MDSC) induced cellular immune deficiency and bone marrow inflammatory microenvironment play an important role in the pathogenesis and progression of myelodysplastic syndrome (MDS), but the underlying mechanism remains unclear. Here, we revealed that immune checkpoint protein TIM3 and CEACAM1 were highly demonstrated on MDSC and CD8 + T cells in MDS patients. CD8 + T cells were reduced in number and function and presented a exhaustion state. The levels of pro-inflammatory cytokines (IL-1β, IL-18) and CEACAM1 were raised in bone marrow supernatants and MDSC culture supernatants. Blocking or neutralizing TIM3/CEACAM1 and IL-1β/IL-18 partially reversed exhaustion of CD8 + T cells. Moreover, TIM3 correlated with NF-κB /NLRP3 inflammatory pathway. The levels of NF-κB/NLRP3/ Caspase-1/IL-1β and IL-18 were all increased in MDSC of MDS. Co-culturing MDSC from MDS patients with rhCEACAM1 enhanced NF-κB/NLRP3/ Caspase-1/IL-1β and IL-18 levels, whereas blocking TIM3 could partially reverse the above manifestations. These results indicated that TIM3/CEACAM1 pathway involved in CD8 + T cells exhaustion and might activate the NF-κB/NLRP3/ Caspase-1 pathway in MDSC, increasing pro-inflammatory cytokines secretion in MDS bone marrow microenvironment. This study provided a basis for applying immune checkpoint inhibitors that could simultaneously modulate proinflammatory cytokine secretion and enhance anti-tumour immune function in the treatment of MDS.

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