瘤内 Treg 拮抗剂对肾癌小鼠的抗转移作用

IF 0.7 4区 农林科学 Q3 VETERINARY SCIENCES Acta veterinaria Hungarica Pub Date : 2024-06-18 Print Date: 2024-07-03 DOI:10.1556/004.2024.01037
Dominik Gulyás, Gábor Kovács, István Jankovics, Máté Hidvégi, Béla Dénes, Lilla Kálfalvy-Molnár, Rebeka Nagypál, Márta Lőrincz
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引用次数: 0

摘要

肿瘤微环境中调节性 T 细胞(Tregs)的相互作用给抗癌免疫疗法带来了巨大挑战。本研究探讨了Treg阻断提高效应T细胞效率的潜力。研究考察了两种不同的治疗鸡尾酒:3p-hpRNA(5'三磷酸发夹RNA)与未甲基化的CpG寡核苷酸(CpG)相结合;CpG与OX40受体特异性单克隆抗体(抗OX40)相结合。将 Renca 细胞(肾皮质细胞腺癌)皮下移植到 30 只 BALB/c 小鼠体内,然后将动物分为三个治疗组:第 1 组:CpG+抗-OX40;第 2 组:CpG+3p-hp;第 3 组:CpG+抗-OX40:CpG+3p-hpRNA,第 3 组:未处理对照组。根据肿瘤生长情况、转移发生率和总存活率评估治疗效果。移植后第 28 天,实验因肿瘤进展而终止。虽然生存时间和原发肿瘤大小的比较变得无关紧要,但组织学检查提供了有价值的见解。我们观察到不同组的原发肿瘤特征存在明显差异:第 1 组和第 2 组的肿瘤呈分界状,而第 3 组的肿瘤呈弥漫性坏死。70%的未治疗小鼠出现明显的肺转移,而两组治疗小鼠均未出现肺转移。我们的研究结果使我们对治疗的潜在疗效充满信心,从而为今后的研究奠定了坚实的基础。
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Antimetastatic effect of intratumoral Treg antagonists in mice with renal cancer.

The interplay of regulatory T cells (Tregs) within the tumour microenvironment presents a significant challenge in anticancer immunotherapy. This study investigates the potential of Treg blockade to enhance the efficiency of effector T cells. Two distinct treatment cocktails were examined: 3p-hpRNA (5' triphosphate hairpin RNA) combined with unmethylated CpG oligonucleotide (CpG); CpG in combination with OX40 receptor-specific monoclonal antibody (anti-OX40). Treatment efficacy was assessed using a murine model of kidney adenocarcinoma.Renca cells (renal cortical cells with adenocarcinoma) were subcutaneously engrafted in 30 BALB/c mice, then animals were allocated into three treatment groups: Group 1: CpG+anti-OX40, Group 2: CpG+3p-hpRNA, Group 3: untreated control. Treatment efficacy was evaluated based on tumour growth, the occurrence of metastases and overall survival.On day 28 post-implantation, experiments had to be terminated due to tumour progression. Although comparisons of survival times and primary tumour sizes thus became inconsequential, histological examinations provided valuable insights. We observed distinct variations in primary tumour characteristics among the different groups: Groups 1 and 2 displayed demarcations, while Group 3 exhibited diffuse tumours with necrosis. Lung metastases were evident in 70% of untreated mice, whereas none were observed in either of the treated groups.Our findings instil confidence in the potential efficacy of the treatments, thereby laying a solid foundation for future investigations.

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来源期刊
Acta veterinaria Hungarica
Acta veterinaria Hungarica 农林科学-兽医学
CiteScore
1.80
自引率
0.00%
发文量
39
审稿时长
>36 weeks
期刊介绍: Acta Veterinaria Hungarica publishes original research papers presenting new scientific results of international interest, and to a limited extent also review articles and clinical case reports, on veterinary physiology (physiological chemistry and metabolism), veterinary microbiology (bacteriology, virology, immunology, molecular biology), on the infectious diseases of domestic animals, on veterinary parasitology, pathology, clinical veterinary science and reproduction.
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