A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

Exploration and validation of the effects of robust co-expressed immune-related genes on immune infiltration patterns and prognosis in laryngeal cancer

ObjectivesLaryngeal cancer is a common malignant tumor that originates from the larynx, yet its molecular mechanisms have not been thoroughly explored. The purpose of this study was to identify and evaluate immune-related genes in laryngeal cancer through gene co-expression networks, which may serve as biomarkers for its immunotherapy.MethodsWe applied ESTIMATE to evaluate the immune-infiltration landscape of tumor microenvironment. The co-expression networks were constructed by weighted gene co expression network analysis (WGCNA) and compared with the existing human immune related genes (IRGs) to determine the co-expressed IRGs. GSVA combined with CIBERSORT and ssGSEA illustrated the correlation of hub genes and immune infiltration patterns. TIDE algorithm and Subclass mapping evaluated the function of hub genes in predicting immune function and immunotherapeutic sensitivity. The pRRophetic was employed in the sensitivity prediction of chemotherapeutic drugs.ResultsA total of 23 co-expressed IRGs were identified and showed robust expression characteristics. These genes were significantly related to immune infiltration patterns, immune function and sensitivity prediction of immunotherapy and chemotherapeutic drugs for laryngeal cancer patients. Genetic alteration in somatic mutation level and related pathways were also revealed.ConclusionThe 23 co-expressed IRGs may act as immunotherapeutic biomarkers and potential therapeutic targets for laryngeal cancer with certain expression robustness. The molecular mechanisms deserve further investigation, which will guide clinical treatment in the future.     

滋阴清热方治疗对甲状腺功能亢进症阴虚火旺证患者疗效、血浆内皮素-1、炎症因子和免疫功能的影响

目的:研究滋阴清热方治疗对甲状腺功能亢进症阴虚火旺证患者疗效、血浆内皮素-1、炎症因子和免疫功能的影响。方法:将广州市花都区妇幼保健院收治的100例甲状腺功能亢进症阴虚火旺证患者分成观察组和对照组。对照组:给患者使用常规药物治疗;观察组:在对照组的基础上,给予滋阴清热方治疗。干预后,比较两组患者的临床疗效、血浆内皮素-1(Endothelin,ET)、炎症因子[白介素-2(Interleukin-2,IL-2)、白介素-8(Interleukin-8,IL-8)]及肿瘤坏死因子(Tumour Necrosis Factor-α,TNF-α)和免疫功能(CD3^+、CD4^+、CD8^+及CD4^+/CD8^+)。结果:干预前,两组患者IL-2、IL-8及TNF-α无变化,差异无统计学意义(P>0.05);干预后,观察组患者的IL-2比对照组高,且对照组的IL-8及TNF-α比观察组的高,P<0.05,差异有统计学意义;干预前,两组患者的CD3^+、CD4^+、CD8^+及CD4^+/CD8^+与ET无变化;干预后,观察组的CD3^+、CD4^+、CD8+及CD4^+/CD8^+比对照组高,P <0.05,差异有统计学意义,且观察组的ET低于对照组且观察组总有效率明显高于对照组。结论:滋阴清热方治疗降低了血浆内皮素-1,减少炎症的出现,提高免疫功能。     

Emerging from their burrow: Hedgehog pathway inhibitors for cancer

Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target.

Areas covered: In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors.

Expert opinion: HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.     

Emodin attenuates acute lung injury in Cecal-ligation and puncture rats

Acute lung injury (ALI) is a major cause of sepsis-induced acute respiratory failure. Emodin has been considered to play a protective role for acute lung edema in cecal ligation and puncture (CLP)-induced sepsis model. In this study we aimed to investigate whether emodin could improve CLP-induced lung sepsis via regulating aquaporin (AQP) and tight junction (TJ), inflammatory factors, and pulmonary apoptosis. The results showed that sepsis-induced pulmonary pathological changes were significantly improved after emodin treatment. Emodin was found to upregulate AQP and TJ expression in the CLP model. Meanwhile, inflammatory cytokine release and pulmonary apoptosis was remarkably reduced after emodin treatment in lung sepsis. Our data demonstrated that emodin could suppresse inflammation, restore pulmonary epithelial barrier and reduce mortality in CLP-induced ALI, suggesting the potential therapeutic application of emodin in sepsis.     

益生菌联合肠内营养对急性胰腺炎患者肠道菌群及外周血miR-155的影响

目的 探讨益生菌联合肠内营养对急性胰腺炎患者肠道菌群及外周血miR-155的影响。 方法 选取2016年6月至2018年12月河北医科大学第二医院消化内科收治的92例急性胰腺炎患者作为研究对象，根据随机数字表法分为观察组（n=46）和对照组（n=46），对照组在常规治疗基础上给予肠内营养治疗，观察组在对照组基础上给予双歧杆菌乳杆菌三联活菌片，观察两组患者治疗前后肠道菌群、炎性介质及血清miR-155变化，比较两组患者治疗后胃肠道功能恢复情况。结果 治疗后，观察组双歧杆菌、乳酸杆菌增加数量，肠球菌、大肠埃希菌减少数量，血清CRP、IL-6、IL-17、TNF-α、miR-155降低水平均显著高于对照组（P<0.05）；观察组患者胃肠生活质量量表（GIQLI）评分高于对照组，腹胀消失时间、腹痛消失时间、肠鸣音恢复时间、血清淀粉酶恢复正常时间均少于对照组（P<0.05）。结论 益生菌联合肠内营养治疗急性胰腺炎可调节肠道菌群平衡，降低血清miR-155水平，缓解炎性反应，促进肠道功能恢复。