Eissa Maha Mohamed, Allam Sonia Rifaat Ahmed, Ismail Cherine Adel, Ghazala Rasha Abdelmawla, El Skhawy Nahla, Zaki Inass Ibrahim Ahmed, Ibrahim Eman Ibrahim El-Said
Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Al-Moassat Medical Campus, Alexandria, Egypt.
Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Eur J Med Res. 2025 Apr 17;30(1):304. doi: 10.1186/s40001-025-02531-5.
Cancer is a global health concern, with millions of new cases and deaths annually. Recently, immunotherapy has strengthened cancer treatment by harnessing the body's immune system to fight cancer. The search for advanced cancer immunotherapies has expanded to explore pathogens like parasites for their potential anti-neoplastic effects. While some parasites have shown promising results, the role of Schistosoma mansoni in breast cancer remains unexplored.
This pre-clinical study investigated the anti-neoplastic potential of autoclaved Schistosoma mansoni antigen against breast cancer. In vitro, autoclaved Schistosoma mansoni antigen was evaluated on the MCF-7 human breast cancer cell line, while in vivo experiments used a chemically induced breast cancer rat model to evaluate tumour growth, liver enzyme levels, and immune response. Histopathological and immunohistochemical analyses assessed changes in tumour tissue, cell proliferation (Ki-67), angiogenesis (CD31), immune cell infiltration (CD8 T cells), regulatory T cells (FoxP3), and programmed death ligand 1 (PD-L1) expression.
In vitro, autoclaved Schistosoma mansoni antigen significantly reduced MCF-7 cell viability in a dose- and time-dependent manner. In vivo, autoclaved Schistosoma mansoni antigen treatment significantly reduced tumour weight and volume, improved liver enzyme levels, increased tumour necrosis, and decreased fibrosis. Immunohistochemical analysis revealed decreased Ki-67 and CD31 expression, indicating reduced cell proliferation and angiogenesis, respectively. Autoclaved Schistosoma mansoni antigen also enhanced immune responses by increasing CD8 T cells infiltration and decreasing FoxP3 expression, resulting in a higher CD8 T cells/FoxP3 ratio within the tumour microenvironment. Notably, PD-L1 expression was also downregulated, suggesting potential immune checkpoint inhibition.
Autoclaved Schistosoma mansoni antigen demonstrated potent anti-neoplastic activity, significantly reducing tumour growth and modulating the immune response within the tumour microenvironment. These results highlight autoclaved Schistosoma mansoni antigen's potential as a novel immunotherapy for breast cancer.
癌症是一个全球性的健康问题，每年有数百万新发病例和死亡病例。最近，免疫疗法通过利用人体免疫系统对抗癌症，加强了癌症治疗。对先进癌症免疫疗法的探索已扩大到研究寄生虫等病原体的潜在抗肿瘤作用。虽然一些寄生虫已显示出有前景的结果，但曼氏血吸虫在乳腺癌中的作用仍未得到探索。
这项临床前研究调查了经高压灭菌的曼氏血吸虫抗原对乳腺癌的抗肿瘤潜力。在体外，对MCF-7人乳腺癌细胞系评估经高压灭菌的曼氏血吸虫抗原，而在体内实验中，使用化学诱导的乳腺癌大鼠模型评估肿瘤生长、肝酶水平和免疫反应。组织病理学和免疫组织化学分析评估肿瘤组织的变化、细胞增殖（Ki-67）、血管生成（CD31）、免疫细胞浸润（CD8 T细胞）、调节性T细胞（FoxP3）和程序性死亡配体1（PD-L1）表达。
在体外，经高压灭菌的曼氏血吸虫抗原以剂量和时间依赖性方式显著降低MCF-7细胞活力。在体内，经高压灭菌的曼氏血吸虫抗原治疗显著降低肿瘤重量和体积，改善肝酶水平，增加肿瘤坏死并减少纤维化。免疫组织化学分析显示Ki-67和CD31表达降低，分别表明细胞增殖和血管生成减少。经高压灭菌的曼氏血吸虫抗原还通过增加CD8 T细胞浸润和降低FoxP3表达增强免疫反应，导致肿瘤微环境中CD8 T细胞/FoxP3比值升高。值得注意的是，PD-L1表达也下调，提示潜在的免疫检查点抑制作用。
经高压灭菌的曼氏血吸虫抗原显示出强大的抗肿瘤活性，显著降低肿瘤生长并调节肿瘤微环境中的免疫反应。这些结果突出了经高压灭菌的曼氏血吸虫抗原作为乳腺癌新型免疫疗法的潜力。
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