Caner Ayse, Sadıqova Aygül, Erdoğan Alper, Namlıses Dünya, Nalbantsoy Ayse, Oltulu Fatih, Toz Seray, Yiğittürk Gürkan, Ozkök Emel, Gunduz Cumhur, Ozbel Yusuf, Haydaroğlu Ayfer
Departments of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Basic Oncology, Ege University, Institute of Health Sciences, Izmir, Turkey.
Breast Cancer. 2020 Nov;27(6):1082-1095. doi: 10.1007/s12282-020-01112-0. Epub 2020 May 29.
Cancer is a major cause of death worldwide and most of the therapeutic approaches are relatively ineffective in eliminating cancer especially due to drug resistance. As an alternative, therapy with live microorganisms can induce a robust proinflammatory and anti-cancer immune response in the microenvironment of the tumor. In the present study, we aimed to establish a model for taking the advantages of immune responses against intracellular protozoan parasites for cancer treatment.
Leishmania infantum and L. tropica were used in our study as agents of visceral and cutaneous forms of the infection, respectively. After establishing 4T1 breast cancer in mice groups, live-attenuated L. infantum (At-Li) and live-attenuated L. tropica (At-Lt) treatments were performed and results were evaluated according to tumor volume, immune markers and histological examination.
Live-attenuated Leishmania strains regressed 4T1-breast cancer in mice and are nonpathogenic, and these strains induce an immune response against 4T1 breast cancer. It is shown that At-Lt is found to be more effective than At-Li in breast cancer treatment using different methods included in the study as analyses of immune parameters, and histopathological examination in tumor tissue besides spleen cells. The tumor grew more slowly by the immune-stimulant effect of live-attenuated Leishmania parasites.
This promising therapy should be investigated for optimization in further studies with different cancer types and L. tropica may be designed to express antigens to enhance tumor antigen-specific responses, which may further improve efficacy and immune memory development.
癌症是全球主要的死亡原因，大多数治疗方法在消除癌症方面相对无效，尤其是由于耐药性。作为一种替代方法，用活微生物进行治疗可在肿瘤微环境中诱导强大的促炎和抗癌免疫反应。在本研究中，我们旨在建立一种利用针对细胞内原生动物寄生虫的免疫反应进行癌症治疗的模型。
在我们的研究中，分别使用婴儿利什曼原虫和热带利什曼原虫作为内脏型和皮肤型感染的病原体。在小鼠组中建立4T1乳腺癌模型后，进行减毒活婴儿利什曼原虫（At-Li）和减毒活热带利什曼原虫（At-Lt）治疗，并根据肿瘤体积、免疫标志物和组织学检查评估结果。
减毒活利什曼原虫菌株使小鼠的4T1乳腺癌消退且无致病性，这些菌株可诱导针对4T1乳腺癌的免疫反应。研究表明，在使用包括免疫参数分析、肿瘤组织及脾细胞的组织病理学检查等本研究中的不同方法进行乳腺癌治疗时，At-Lt比At-Li更有效。减毒活利什曼原虫寄生虫的免疫刺激作用使肿瘤生长更缓慢。
这种有前景的治疗方法应在进一步针对不同癌症类型的研究中进行优化研究，并且热带利什曼原虫可设计用于表达抗原以增强肿瘤抗原特异性反应，这可能会进一步提高疗效和免疫记忆的形成。
