Correlation between circulating myeloid-derived suppressor cells and Th17 cells in esophageal cancer

AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P < 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.

Changes in the frequency of myeloid-derived suppressor cells after transarterial chemoembolization with gelatin sponge microparticles for hepatocellular carcinoma

Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells(MDSCs)have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM–TACE to evaluate the effect on the immune function of HCC patients.Methods: Eight patients diagnosed with HCC underwent GSM–TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China;we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry(FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery.Results: MDSC frequency after GSM–TACE had a significant downward trend. Pre-TACE, it was 30.73% ? 11.93%,decreasing to 18.60% ? 11.37% at 10 days after operation. This decrease was not statistically significant(P > 0.05). MDSC frequency was even lower 30 days after TACE(7.63% ? 7.32%) than at 10 days after TACE(P < 0.05), and there was a significant difference compared with pre-TACE(P < 0.001). We evaluated tumor response at 30 days after GSM–TACE according to the Modified Response Evaluation Criteria in Solid Tumors(mRECIST), and all eight patients showed partial response(PR).Conclusion: Our results confirmed that GSM–TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.

The possible role and clinical implication of myeloid-derived suppressor cells in the peripheral blood of patients with hepatitis B virus-related acute-on-chronic liver failure

Objective To explore the possible role and clinical implications of myeloid-derived suppressor cells(MDSC)in the peripheral blood of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBVACLF).Methods A total of 25 HBV-ACLF patients

Single-cell transcriptome profiling of sepsis identifies HLA-DR^(low)S100A^(high)monocytes with immunosuppressive function

Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.Methods We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis.Flow cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein level.To interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative assay.Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.Results scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic patients.We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive function.By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human sepsis.Moreover,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.Conclusions This study identifies HLA-DR^(low)S100A^(high)monocytes correlated with immunosuppressive state upon septic challenge,inhibition of which can markedly mitigate sepsis-induced immune depression,thereby providing a novel therapeutic strategy for the management of sepsis.

黄芪多糖对肺癌外周循环MDSC的影响及临床效果研究

目的综合分析黄芪多糖对肺癌外周循环MDSC(髓系抑制性细胞)的影响及临床效果。方法选取2013年1月~2016年10月间我院收治的126例肺癌患者,按照入院顺序随机分为实验组与对照组,每组63例。对照组应用单纯化疗方法,实验组在对照组基础上应用黄芪多糖。统计分析两组患者的肿瘤坏死因子α(TNF-α)水平、外周循环髓系抑制性细胞水平、白细胞介素-6(IL-6)水平、临床治疗总有效率等指标。结果实验组患者治疗总有效率为66.67%(42/63),对照组患者治疗总有效率为41.27%(26/63),实验组患者治疗总有效率显著高于对照组(P<0.05);治疗前,两组患者的肿瘤坏死因子α水平、外周循环髓系抑制性细胞水平、白细胞介素-6水平比较无统计学意义(P>0.05);治疗后,实验组患者的肿瘤坏死因子α水平、外周循环髓系抑制性细胞水平、白细胞介素-6水平显著优于对照组患者(P<0.05)。结论黄芪多糖能够有效降低肺癌外周循环髓系抑制性细胞水平,不断改善免疫功能,提高临床治疗总有效率。

髓系抑制细胞、Th17细胞在哮喘患儿外周血中的表达

目的分析髓系抑制细胞(MDSCs)及Th17细胞在哮喘患儿外周血中的表达情况和临床意义。方法选取自贡市第一人民医院儿科2013年6月至2015年8月收治的120例哮喘患儿作为观察组,另外选择87例健康儿童作为对照组。应用流式细胞术检测MDSCs、Th17细胞在哮喘患儿外周血中的表达情况。结果和对照组相比,观察组MDSCs占有核细胞的百分比和Th17细胞占单个核细胞的百分比都显著升高(Hc值分别为56.14、45.98,均P<0.05),差异具有统计学意义。结论从M DSCs、Th17细胞在哮喘患儿外周血中的表达情况来看,它们可能参与了婴幼儿哮喘的发生与发展过程。

髓源性抑制细胞在妊娠过程中的变化及作用

目的探索髓源性抑制细胞(MDSC)在妊娠过程中的变化以及免疫抑制作用,为母胎免疫耐受调控提供理论基础。方法选取2014年1~12月在我院行产检的正常妊娠妇女共106例作为研究对象,孕早、中、晚期孕妇分别为24、29、32例,产妇21例。对照组为于我院行孕前检查的正常妇女,无流产史及其他基础疾病,共34例。分别采集孕早期、中期、晚期外周血以及产妇生产时外周血、脐带血、胎盘以及蜕膜组织、产后24h外周血进行检测。孕早、中、晚期孕妇分别为24、29、32例,产妇为21例。对照组为于我院行孕前检查的正常妇女,无流产史及其他基础疾病,共34例。采用流式细胞仪技术检测MDSC的比例,分析MDSC的变化。采用流式分选、纯化后的MDSC,与CD3+T细胞共培养,通过分析[3 H]胸(腺嘧啶脱氧核)苷密度分析T细胞增殖能力。结果妊娠妇女外周血MDSC的比例(6.25±3.59)%显著高于未妊娠正常女性(1.70±0.77)%(P<0.01),而孕中期外周血MDSC比例(10.43±7.22)%显著高于孕早期(3.88±1.67)%、晚期(5.25±1.91)%(P<0.01);分娩后,外周血MDSC比例(1.81±1.08)%下降至妊娠前水平。脐带血、蜕膜以及胎盘组织中MDSC的比例也维持在较高水平,脐带血MDSC比例(17.15±6.00)%显著高于蜕膜(8.65±3.67)%及胎盘(7.66±3.73)%(P<0.01)。MDSC显著抑制外周血CD3+T细胞增殖能力(P<0.01)。结论 MDSC可能参与了母胎免疫耐受的调节,抑制母体免疫排斥反应,有利于妊娠继续维持。

荷瘤乳腺癌女性外周血髓样来源抑制性细胞表达浓度及意义分析

目的:分析荷瘤乳腺癌女性外周血髓样来源抑制性细胞(MDSC)表达浓度及意义。方法:连续选取2015年1月至2016年12月经我院肿瘤外科初次确诊的女性乳腺癌患者41例,入选对象均未接受过各种治疗。对照组选择同期参加我院医院体检结论健康志愿者26例。乳腺癌组在开始治疗前接受了外周血MDSC(CD11b+、CD33+、CD14-)表达浓度检测,对照组在体检期间接受了相同检查。结果:荷瘤乳腺癌女性患者外周血MDSC表达浓度明显高于对照组,不同年龄荷瘤乳腺癌女性外周血MDSC表达浓度均明显高于相同年龄对照组(P均<0.001)。不同临床表现荷瘤乳腺癌女性外周血MDSC表达浓度比较中,肿瘤淋巴结转移(TNM)Ⅲ期组外周血MDSC表达浓度明显高于TNMⅠ期和Ⅱ期组(P<0.01),而年龄小组与年龄大组外周血MDSC表达浓度分布无明显区别(P>0.05)。不同病理情况荷瘤乳腺癌女性外周血MDSC表达浓度比较中,淋巴结转移组外周血MDSC表达浓度明显高于无淋巴结转移组(P<0.01),而肿瘤体积小组与肿瘤体积大组、组织学Ⅰ级和Ⅱ级组与组织学Ⅲ级组外周血MDSC表达浓度分布均无明显区别(P均>0.05)。不同分子学分型荷瘤乳腺癌女性外周血MDSC表达浓度比较中,Luminal A、Luminal B、HER-2过表达型和三阴乳腺癌等分子学分型荷瘤乳腺癌女性外周血MDSC表达浓度分布均无明显区别(P均>0.05)。结论:外周血MDSC可作为乳腺癌生物学辅助诊断特异性标识,且与乳腺癌临床TNM分期以及有无淋巴结转移关系密切。

Neutrophils in cancer—unresolved questions

There is growing recognition that neutrophils play an important role in cancer initiation, progression and metastasis. Although they are typically characterized as short-lived effector cells, neutrophils have been shown to acquire immunosuppressive and pro-tumorigenic functions that promote tumor progression and escape. As such, inhibition of their function or depletion of neutrophils are being explored as potential cancer therapies. However, growing evidence of neutrophil diversification in cancer and their potential anti-tumor roles raise many unresolved questions. Here, we review recent advances that address the definition,origin and function of neutrophils in cancer, and elaborate on obstacles that make the study of neutrophils challenging. We envision that this review will provide the groundwork for focused design of therapeutics that will specifically target "tumorreprogrammed" neutrophils while sparing normal neutrophils to improve patient outcomes.