Ardeshiri Keivan, Hassannia Hadi, Ghalamfarsa Ghasem, Jafary Hanieh, Jadidi Farhad
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
IUBMB Life. 2025 Jan;77(1):e2933. doi: 10.1002/iub.2933.
Targeting the influencing factors in tumor growth and expansion in the tumor microenvironment is one of the key approaches to cancer immunotherapy. Various factors in the tumor microenvironment can in cooperation stimulate tumor growth, suppress anti-tumor immune responses, promote drug resistance, and ultimately enhance tumor recurrence. Therefore, due to the dependence and close cooperation of these axes, their combined targeting can have a greater effect compared to their individual targeting. Among the important factors affecting tumor growth in the tumor region, CD73 and EGFR play an important role in tumor growth by stimulating each other's expression and function. Therefore, we intended to use the nanocarriers that we had previously produced and characterized to deliver anti-CD73 and EGFR siRNAs to murine breast cancer 4T1 cells. Silencing CD73 and EGFR could significantly induce cell death in cancer cells. Downregulation of the CD73/EGFR axis also suppressed the migratory and proliferative potential of cancer cells. This therapeutic strategy also inhibited tumor growth in in ovo model. These findings imply that simultaneous targeting of CD73 and EGFR in breast cancer can be considered a novel immunotherapeutic approach that needs further investigation in future studies.
针对肿瘤微环境中影响肿瘤生长和扩散的因素是癌症免疫治疗的关键方法之一。肿瘤微环境中的各种因素可协同刺激肿瘤生长、抑制抗肿瘤免疫反应、促进耐药性，并最终增强肿瘤复发。因此，由于这些轴的依赖性和密切合作，与单独靶向相比，联合靶向它们可能具有更大的效果。在影响肿瘤区域肿瘤生长的重要因素中，CD73和表皮生长因子受体（EGFR）通过相互刺激表达和功能在肿瘤生长中起重要作用。因此，我们打算使用我们之前制备并表征的纳米载体，将抗CD73和EGFR小干扰RNA（siRNAs）递送至小鼠乳腺癌4T1细胞。沉默CD73和EGFR可显著诱导癌细胞死亡。CD73/EGFR轴的下调也抑制了癌细胞的迁移和增殖潜能。这种治疗策略在鸡胚模型中也抑制了肿瘤生长。这些发现表明，同时靶向乳腺癌中的CD73和EGFR可被视为一种新型免疫治疗方法，未来研究需要进一步探究。
