Composition and plasticity of triple-negative breast carcinoma-infiltrating regulatory T cells

Low Foxp3⁺ regulatory T-cell (Treg) presence in the tumor-infiltrating lymphocytes (TILs) is considered favorable in breast cancer, and numerous CD25-targeting agents have been applied in the attempt to remove Foxp3⁺ Treg cells, which typically present CD4⁺CD25^+/hi surface phenotype. However, CD25 is not Treg-exclusive and can be upregulated by effector T cells. Hence, CD25 depletion may cause the elimination of activated T cells that are responding to tumor-specific antigens. In this study, the composition and function of CD4⁺CD25⁺ cells inside the microenvironment of triple-negative breast carcinoma (TNBC) were investigated. Directly ex vivo, the Foxp3⁺ Treg cells represented a minor subset in total CD4⁺CD25⁺ TILs. Significant differences were observed in the expression of Treg-associated molecules between CD4⁺CD25⁺Foxp3⁺ TILs and CD4⁺CD25⁺Foxp3⁻ TILs. While both the CD4⁺CD25⁺Foxp3⁺ and the CD4⁺CD25⁺Foxp3⁻ TILs could express CTLA-4 and LAG-3, the expression levels were significantly higher in CD4⁺CD25⁺Foxp3⁺ TILs than in CD4⁺CD25⁺Foxp3⁻ TILs. Upon TCR stimulation, the expression of TGF-beta was significantly higher in CD4⁺CD25⁺Foxp3⁺ TILs, while the expression of IL-10 was significantly higher in CD4⁺CD25⁺Foxp3⁻ TILs. These differences were conserved in the blood counterparts of these cells. Interestingly, the level of CD25⁺Foxp3⁺ cells in circulating CD4⁺ T cells was positively correlated with the level of CD25⁺Foxp3⁺ cells in CD4⁺ TILs, but the level of CD25⁺Foxp3⁻ cells in circulating CD4⁺ T cells was not associated with the level of CD25⁺Foxp3^- cells in CD4⁺ TILs. Th17-polarizing medium could readily remodel CD4⁺CD25⁺Foxp3⁻, but not CD4⁺CD25⁺Foxp3⁺, T cells into RORgammat and IL-17-expressing T cells, demonstrating stronger plasticity of the former subset. Together, these data demonstrated that the CD4⁺CD25⁺ TILs were composed of distinctive Foxp3⁻ and Foxp3⁺ cells, with the former representing the major subset. The antigen specificity and effector molecule expression of the CD4⁺CD25⁺Foxp3⁻ thus require further analyses.     

Clinical and pathological features in adult-onset NIID patients with cortical enhancement

Journal of Neurology - Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in multiple organs. On...     

下调FAM111B对乳腺癌细胞增殖和凋亡的影响

目的:探讨下调FAM111B对乳腺癌细胞系MDA-MB-231和MCF7细胞增殖和凋亡的影响及其机制。方法:构建siR-FAM111B慢病毒载体,转染乳腺癌MDA-MB-231和MCF7细胞,qRT-PCR检查转染组与对照组FAM111B mRNA表达,Western blotting法检测各组细胞FAM111B蛋白表达。用CCK-8法检测细胞的增殖能力。流式细胞术检测Annexin-V/PI双染各组细胞的凋亡情况。Western blotting法检测凋亡相关蛋白Bax和Bcl-2的表达。结果:siR-FAM111B成功转染MDA-MB-231和MCF7细胞,转染后应用qRT-PCR和Western blotting检测,结果显示,FAM111B mRNA与蛋白水平均下调。siR-FAM111B能抑制两种细胞的增殖。Annexin-V/PI双染结果显示,下调FAM111B诱导两种细胞凋亡。Western blotting结果显示,下调FAM111B可以促进两种细胞Bax的表达,抑制Bcl-2的表达。结论:下调FAM111B能够抑制乳腺癌细胞的增殖,通过调节线粒体凋亡通路诱导细胞凋亡。     

严重急性呼吸综合征冠状病毒2流行期间儿童实体肿瘤诊治中的防控策略

自2019年12月湖北出现新型冠状病毒感染(corona virus disease 2019,COVID-19)患者以来,该病毒现已逐步扩散至全国各地及境外多个国家。国际病毒分类委员会将致病病毒命名为严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2),人群普遍易感,包括儿童和孕产妇。恶性实体肿瘤患儿因肿瘤本身及化疗、放疗、免疫治疗等综合治疗手段的影响,免疫力较正常儿童低,可能更容易发生感染并进展为重症病例,而保障恶性实体肿瘤综合治疗计划实施的延续性和规范性是提高疗效、获得良好预后的关键之一。疫情期间,如何在做好疫情防控工作的同时保障肿瘤诊疗工作有序进行,是摆在每一个病患和医务人员面前的难题。本文结合COVID-19的传播特点以及有关部门防控COVID-19的要求,针对儿童实体肿瘤诊疗工作中的主要环节,提出疫情期间应考虑实施的措施和策略,建议制定科学的实体肿瘤门诊和病房管理制度,保障急诊手术,合理安排限期手术,适当延期择期手术,保障化疗规律进行,在保护患儿免受SARS-CoV-2感染的同时,确保儿童实体肿瘤综合诊疗工作的连续性。