儿童指突状树突细胞肉瘤合并骨髓增生异常综合征一例报告并文献复习

指突状树突细胞肉瘤(interdigitating dendritic cell sarcoma,IDCS)是一种罕见的树突状细胞肿瘤,目前全球仅百余例报道,常以无痛性淋巴结肿大起病,侵袭性较强、预后较差[1-2]。骨髓增生异常综合征(myelodysplastic syndromes,MDS)为起源于造血干、祖细胞的恶性克隆性疾病,以单系或多系病态造血、易向白血病转化为特征,目前被认为是一种老年性疾病[3]。本研究报道1例同患IDCS和MDS的患儿,为国内外首次报道2种肿瘤同时发生,旨在探讨2种肿瘤的诊治要点,避免漏诊、误诊。     

Dendritic cells can prime anti-tumor CD8+ T cell responses through major histocompatibility complex cross-dressing

1. Download : Download high-res image (125KB)
2. Download : Download full-size image

     

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Dysplastic naevi (DN) are benign lesions with atypical features intermediate between that of common melanocytic naevi (CMN) and malignant melanoma (MM). Debate remains over whether DN represent progressive lesions from CMN. Through gene expression profiling and analysis of molecular gene signatures, our study revealed progressive increases in immune activation and regulation, along with pathways implicated in melanomagenesis, from CMN to DN to MM. Using criteria of 1.5‐fold change and false discovery rate ≤0.05, we found differential expression of 7186 probes (6370 unique genes) with the largest difference detected between DN and MM from the standpoint of genomic melanoma progression. Despite progressive increases in the T‐helper type 1 (Th1)‐inducing gene (IL‐12), RT‐PCR indicated impaired Th1 or cytotoxic T‐cell response (decreased IFN‐γ) in MM. Concordantly, our results indicated progressive increases in molecular markers associated with regulatory T cells, exhausted T cells and tolerogenic dendritic cells, including detection of increased expression of suppressor of cytokine signalling 3 (SOCS3) in dendritic cells associated with MM. All together, our findings suggest that the increased immunosuppressive microenvironment of melanoma may contribute to unhampered proliferation of neoplastic cells. In addition, the detection of increased markers associated with tolerogenic dendritic cells in MM suggests that targeting these suppressive immune cell types may represent an alternative avenue for future immunotherapy.     

急性乙型肝炎患者pDCs上CD86表达变化及意义

目的 探讨外周血浆细胞样树突状细胞(pDCs)在急性乙型肝炎(AHB）患者临床转归中的变化及作用。方法 纳入2015年6月至2017年5月收治的急性乙型肝炎(AHB组)患者40例， 给予退黄、降酶、保肝等药物，并加用恩替卡韦0．5 mg空腹口服，1次/d。另纳入健康体检者26例为健康对照组（ HC组）。HC组于体检当天、AHB组于治疗前及治疗后6周采集外周静脉全血，采用ELISA法检测2组血浆HBV DNA、HBsAg、HbeAg及肝功能指标水平，并应用流式细胞仪检测pDCs的频数及其功能分子CD86的表达水平。结果 治疗6周后，AHB组临床症状显著缓解，血清学指标和乙型肝炎标志物水平显著下降（P<0.01）。治疗6周后，AHB组HBV DNA转阴率为82.5%，HBsAg清除率为72.5%，HBeAg血清学转换率为75.0%，与治疗前比较差异均有统计学意义（P<0.01）, HC组pDCs频数显著高于AHB组治疗前。AHB组治疗后CD86+pDCs显著高于治疗前。HC组CD86ABC显著低于AHB组治疗前。结论 在急性乙型肝炎患者外周血pDCs的数量降低。急性乙型肝炎患者在治疗后CD86+pDCs增多。急性乙型肝炎患者pDCs上CD86表达上调。     

化瘀解毒汤对脓毒血症APACHEⅡ评分、ISTH DIC评分及外周血树突状细胞表面物质表达水平的影响

目的探讨化瘀解毒汤对脓毒血症患者APACHEⅡ评分、ISTH DIC评分及外周血树突状细胞表面物质表达水平的影响。方法将66例脓毒症患者随机分为对照组和化瘀解毒组,每组33例。对照组给予抗感染、补充血容量、积极治疗原发疾病、吸氧等综合治疗,化瘀解毒组在上述基础上加用化瘀解毒汤治疗,每日1剂,持续治疗2周。检测血清炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、降钙素原(PCT)]水平变化,应用急性生理与慢性健康状况评分Ⅱ(APACHEⅡ)、DIC评分评估脓毒症患者病情严重程度,应用流式细胞仪分析树突状细胞相关表面分子CD80、CD83、CD86表达情况,比较临床疗效。结果与治疗前比较,两组血清IL-6、TNF-α、PCT水平均降低(P<0.01),APACHEⅡ评分、ISTH DIC评分均降低(P<0.01),CD80、CD86水平均降低(P<0.01),CD83水平无差异(P>0.05);与对照组比较,化瘀解毒组血清IL-6、TNF-α、PCT水平均较低(P<0.01),APACHEⅡ评分、ISTH DIC评分均较低(P<0.01),CD80、CD86水平均较低(P<0.01),总有效率较高(P<0.01)。结论化瘀解毒汤辅助治疗脓毒血症疗效显著,可有效降低APACHEⅡ评分、ISTH DIC评分,可能与调节外周血树突状细胞表面物质表达有关。     

红景天苷通过TLR4调控DC提高T细胞对肺癌3LL细胞的杀伤力

目的：探讨红景天苷（salidroside，SAL）对树突状细胞（dendritic cell，DC）表型及细胞毒性T细胞（cytotoxic T lympho‐cyte，CTL）抗肿瘤能力的影响。方法：选用Lewis肺癌细胞株3LL、野生型C57BL/6和TLR4-/-C57BL/6小鼠，获取小鼠骨髓来源的DC前体细胞，经过培养分化成未成熟DC，收获第6天的DC，经磁珠分选后获得纯度较高的CD11c+DC。将细胞分成PBS组、SAL组和脂多糖（lipopolysaccharide，LPS）组，培养48 h后用流式细胞术检测SAL体外对DC表面分子、吞噬功能、TLR4通路和对T细胞杀伤能力的影响。结果：与 PBS 组比较，SAL组DC的表面分子CD80、CD86、MHC Ⅱ表达水平显著升高（均 P<0.05）、吞噬功能显著下降（P<0.05）、TLR4 表达水平显著升高（P<0.01）；与野生型组比较，TLR4-/-组DC经SAL或LPS处理后，其表面分子CD80、CD86、MHC Ⅱ的表达水平显著降低（均P<0.05）；与PBS组比较，SAL组刺激活化的CTL对肺癌3LL细胞的杀伤效应显著升高（P<0.05）。结论：SAL可以通过调控TLR4诱导DC成熟，从而提高T细胞的杀伤能力     

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.     

Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation

Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT). When myeloablated BALB/c MyD88 knock-out recipients were transplanted with C57BL/6 (B6) donor cells, they developed significantly more severe GVHD than wild-type (WT) BALB/c hosts. The increased morbidity and mortality in MyD88^–/– mice correlated with increased serum levels of lipopolysaccharide and elevated inflammatory cytokines in GVHD target organs. Additionally, MyD88 deficiency in BMT recipients led to increased donor T cell expansion and more donor CD11c⁺ cell intestinal infiltration with apoptotic cells but reduced proliferation of intestinal epithelial cells compared with that in WT BMT recipients. Decreased expression of tight junction mRNA in epithelial cells of MyD88^–/– mice suggested that MyD88 contributes to intestinal integrity. Cox-2 expression in the GVHD-targeted organs of WT mice is increased upon GVHD induction, but this enhanced expression was obviously inhibited by MyD88 deficiency. The present findings demonstrate an unexpected role for host MyD88 in preventing GVHD after allogeneic BMT.