消化系统肿瘤在我国的发病率高且存活率低,尽管随着医学的不断发展,目前的治疗手段能够在一定程度上提高和改善患者的生存率及预后,但总的生存率仍没有达到人们预期。肿瘤微环境(TME)由多种免疫细胞组成,其中髓源抑制细胞(MDSCs)是起免...消化系统肿瘤在我国的发病率高且存活率低,尽管随着医学的不断发展,目前的治疗手段能够在一定程度上提高和改善患者的生存率及预后,但总的生存率仍没有达到人们预期。肿瘤微环境(TME)由多种免疫细胞组成,其中髓源抑制细胞(MDSCs)是起免疫抑制作用的重要组成部分,它通过抑制机体的免疫细胞如T细胞或者自然杀伤细胞(NK细胞)来帮助肿瘤细胞发生免疫逃逸。研究发现MDSCs的生成、分化、数量及凋亡与消化系统肿瘤的发生发展密切相关,并且靶向MDSCs可作为消化系统肿瘤靶向治疗的潜在靶点,因此本文就MDSCs在消化系统肿瘤中的作用及其靶向治疗的研究做一综述。The incidence rate of digestive system tumors in China is high and the survival rate is low. With the continuous development of medicine, the current treatment methods can improve the survival rate and prognosis of patients, but the overall survival rate still does not meet patient expected. The tumor microenvironment (TME) is composed of various immune cells, myeloid derived suppressor cells (MDSCs) are one kind of important immune suppression cells. They help tumor cells escape by inhibiting immune cells such as T cells or natural killer cells (NK cells). Research has found that the generation, differentiation, quantity, and apoptosis of MDSCs are closely related to the occurrence and development of digestive system tumors, and targeting MDSCs can be a potential point for targeted therapy. Therefore, this paper reviews the role of MDSCs in digestive system tumors and their targeted therapy research.展开更多
[目的]探讨西黄丸对三阴性乳腺癌肺转移的机制。[方法]构建三阴性乳腺癌4T1-BALB/c原位荷瘤小鼠,流式细胞术检测荷瘤小鼠血液、骨髓、肺组织内骨髓源性抑制细胞(MDSCs);通过苏木精-伊红(HE)染色确定小鼠肺转移微环境形成时间;利用蛋白...[目的]探讨西黄丸对三阴性乳腺癌肺转移的机制。[方法]构建三阴性乳腺癌4T1-BALB/c原位荷瘤小鼠,流式细胞术检测荷瘤小鼠血液、骨髓、肺组织内骨髓源性抑制细胞(MDSCs);通过苏木精-伊红(HE)染色确定小鼠肺转移微环境形成时间;利用蛋白质印迹(Western blotting)检测肺组织相关蛋白水平;通过对比各组小鼠肺转移微环境形成时间、肺组织骨髓及外周血中MDSCs数量、肺转移结节、肺转移组织相关蛋白探究西黄丸对乳腺癌肺转移的作用及机制。[结果]西黄丸及乳香、没药药对均在第14天对移植瘤有显著抑制作用;西黄丸能够延长乳腺癌肺转移出现时间(17 d vs. 14 d),且可以显著减少乳腺癌肺转移结节灶的数量;西黄丸能够抑制4T1-BALB/c荷瘤小鼠外周血及肺组织中MDSCs数量,且显著降低肺组织中基质金属蛋白酶9(MMP9)、S100A8/A9表达量。[结论]西黄丸可通过调控外周血及肺组织中MDSCs数量,抑制MMP9、S100A8/A9表达重塑乳腺癌肺转移微环境形成,达到抑制乳腺癌肺转移目的。研究为西黄丸临床抗肿瘤转移应用奠定基础。展开更多
Myeloid-derived suppressor cells(MDSCs)are a group of heterogeneous immature cells with a strong immunosuppressive function in myeloid cells,which are impeded in the differentiation of myeloid cells under the patholog...Myeloid-derived suppressor cells(MDSCs)are a group of heterogeneous immature cells with a strong immunosuppressive function in myeloid cells,which are impeded in the differentiation of myeloid cells under the pathological conditions of hypoxia,inflammation,infection,and cancer.As individuals age,there is a significant increase in myeloid-derived suppressor cells(MDSCs),which subsequently enhance the immunosuppressive functions of Tregs(regulatory T cells)and Bregs(regulatory B cells).Therefore,MDSC may be related to immune system remodeling,thereby preventing excessive lesions caused by aging.This indicates that MDSC could serve as a potent inducer of immune senescence.Immune senescence,characterized by immune dysfunction with aging,is closely linked to the onset of diseases like infections,pulmonary fibrosis,and tumors.To achieve the purpose of anti-aging by intervening in immune aging and slow down the occurrence and development of related diseases.Therefore,understanding the biological characteristics of MDSC and its role in immune aging is crucial for immunotherapy targeting MDSC.This article reviews the different roles of MDSC in immune aging and its relationship with pulmonary fibrosis,tumor and other related diseases to provide theoretical basis for more comprehensive targeted MDSC immunotherapy.展开更多
文摘消化系统肿瘤在我国的发病率高且存活率低,尽管随着医学的不断发展,目前的治疗手段能够在一定程度上提高和改善患者的生存率及预后,但总的生存率仍没有达到人们预期。肿瘤微环境(TME)由多种免疫细胞组成,其中髓源抑制细胞(MDSCs)是起免疫抑制作用的重要组成部分,它通过抑制机体的免疫细胞如T细胞或者自然杀伤细胞(NK细胞)来帮助肿瘤细胞发生免疫逃逸。研究发现MDSCs的生成、分化、数量及凋亡与消化系统肿瘤的发生发展密切相关,并且靶向MDSCs可作为消化系统肿瘤靶向治疗的潜在靶点,因此本文就MDSCs在消化系统肿瘤中的作用及其靶向治疗的研究做一综述。The incidence rate of digestive system tumors in China is high and the survival rate is low. With the continuous development of medicine, the current treatment methods can improve the survival rate and prognosis of patients, but the overall survival rate still does not meet patient expected. The tumor microenvironment (TME) is composed of various immune cells, myeloid derived suppressor cells (MDSCs) are one kind of important immune suppression cells. They help tumor cells escape by inhibiting immune cells such as T cells or natural killer cells (NK cells). Research has found that the generation, differentiation, quantity, and apoptosis of MDSCs are closely related to the occurrence and development of digestive system tumors, and targeting MDSCs can be a potential point for targeted therapy. Therefore, this paper reviews the role of MDSCs in digestive system tumors and their targeted therapy research.
文摘[目的]探讨西黄丸对三阴性乳腺癌肺转移的机制。[方法]构建三阴性乳腺癌4T1-BALB/c原位荷瘤小鼠,流式细胞术检测荷瘤小鼠血液、骨髓、肺组织内骨髓源性抑制细胞(MDSCs);通过苏木精-伊红(HE)染色确定小鼠肺转移微环境形成时间;利用蛋白质印迹(Western blotting)检测肺组织相关蛋白水平;通过对比各组小鼠肺转移微环境形成时间、肺组织骨髓及外周血中MDSCs数量、肺转移结节、肺转移组织相关蛋白探究西黄丸对乳腺癌肺转移的作用及机制。[结果]西黄丸及乳香、没药药对均在第14天对移植瘤有显著抑制作用;西黄丸能够延长乳腺癌肺转移出现时间(17 d vs. 14 d),且可以显著减少乳腺癌肺转移结节灶的数量;西黄丸能够抑制4T1-BALB/c荷瘤小鼠外周血及肺组织中MDSCs数量,且显著降低肺组织中基质金属蛋白酶9(MMP9)、S100A8/A9表达量。[结论]西黄丸可通过调控外周血及肺组织中MDSCs数量,抑制MMP9、S100A8/A9表达重塑乳腺癌肺转移微环境形成,达到抑制乳腺癌肺转移目的。研究为西黄丸临床抗肿瘤转移应用奠定基础。
基金supported by S&T Program of Hebei(No.23379902L).
文摘Myeloid-derived suppressor cells(MDSCs)are a group of heterogeneous immature cells with a strong immunosuppressive function in myeloid cells,which are impeded in the differentiation of myeloid cells under the pathological conditions of hypoxia,inflammation,infection,and cancer.As individuals age,there is a significant increase in myeloid-derived suppressor cells(MDSCs),which subsequently enhance the immunosuppressive functions of Tregs(regulatory T cells)and Bregs(regulatory B cells).Therefore,MDSC may be related to immune system remodeling,thereby preventing excessive lesions caused by aging.This indicates that MDSC could serve as a potent inducer of immune senescence.Immune senescence,characterized by immune dysfunction with aging,is closely linked to the onset of diseases like infections,pulmonary fibrosis,and tumors.To achieve the purpose of anti-aging by intervening in immune aging and slow down the occurrence and development of related diseases.Therefore,understanding the biological characteristics of MDSC and its role in immune aging is crucial for immunotherapy targeting MDSC.This article reviews the different roles of MDSC in immune aging and its relationship with pulmonary fibrosis,tumor and other related diseases to provide theoretical basis for more comprehensive targeted MDSC immunotherapy.
文摘目的探讨膀胱癌MB49细胞来源的外泌体(exosomes)对MDSCs细胞扩增、活化的影响及机制。方法用超滤联合蔗糖重水密度梯度离心法分离纯化膀胱癌MB49细胞分泌的exosomes;电镜形态学分析及Western blotting鉴定;流式细胞仪检测MDSCs比例;ELISA检测VEGF和IL-6;RT-PCR和Western blotting检测cyclin D1、Arg-1 m RNA和蛋白的表达;Western blotting检测p-STAT3和p-NF-κB的变化。结果成功分离纯化得到膀胱癌MB49细胞分泌的exosomes。exosomes可促进MDSCs扩增及活化。实验组MDSCs比例明显升高;Cyclin D1及Arg-1 m RNA和蛋白的表达均上调;p-STAT3和p-NF-κB的表达也上调。结论膀胱癌MB49细胞来源的exosomes能促使MDSCs细胞扩增、活化。研究和分析MDSCs的免疫抑制机制,为疾病的治疗寻找行之有效的新靶点。
