Evgenii Skurikhin, Mariia Zhukova, Natalia Ermakova, Edgar Pan, Darius Widera, Lubov Sandrikina, Lena Kogai, Nikolai Kushlinskii, Aslan Kubatiev, Sergey Morozov, Alexander Dygai
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引用次数: 0
摘要
背景:了解与年龄相关的癌变特征以及细胞免疫的重要性,对于开发针对特定患者群体的有效抗肿瘤疗法至关重要:在这项研究中,我们检测了 "年轻"(8-10周)和 "衰老"(80-82周)C57BL/6雄性小鼠体内癌症干细胞(CSCs)和循环肿瘤细胞(CTCs)的不同群体。我们利用路易斯肺癌(LLC)的正位模型,评估了通过重编程 CD8 阳性 T 细胞(rCD8+ T 细胞)对两种不同年龄小鼠肺癌进行细胞治疗的效果:结果:研究结果表明,随着年龄的增长,肿瘤进展的主要原因是T细胞招募到肺部的能力受损。此外,与年龄较大的小鼠相比,年龄较小的小鼠体内观察到的 CTC 和 CSC 数量较少。研究发现,rCD8+ T细胞对老年小鼠的抗肿瘤效果不如年轻小鼠,这可能是由于治疗对特定CSCs群体的影响减弱所致:这些结果为利用 rCD8+ T 细胞治疗肺癌提供了新的见解。考虑到影响疾病进展的年龄相关特征,这种疗法有可能显著提高治疗方法的有效性。
Age-related features of lung cancer treatment using reprogrammed CD8 positive T cells in mice subjected to injection of Lewis lung carcinoma cells.
Background: Awareness of age-related features of carcinogenesis and the importance of cellular immunity is crucial for developing effective antitumor therapies for specific patient groups.
Methods: In this study, we examined different populations of cancer stem cells (CSCs) and circulating tumor cells (CTCs) in "young" (8-10 weeks) and "aged" (80-82 weeks) C57BL/6 male mice. We used an orthotopic model of Lewis lung carcinoma (LLC) to evaluate the effectiveness of cell therapy targeting lung cancer through reprogrammed CD8-positive T cells (rCD8+ T cells) in mice from two different ages.
Results: The findings revealed that tumor progression with age is primarily caused by impaired recruitment of T cells to the lungs. Additionally, a lower number of CTCs and CSCs were observed in younger mice compared to the older mice. The antitumor effect of rCD8+ T cells in aged mice was found to be inferior to that in young mice, which can be attributed to the reduced impact of therapy on specific CSCs populations.
Conclusions: These results offer new insights into the treatment of lung cancer using rCD8+ T cells. Considering the age-related characteristics influencing disease progression, this therapy has the potential to significantly enhance the effectiveness of treatment methods.