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在注射Lewis肺癌细胞的小鼠中使用重编程CD8阳性T细胞进行肺癌治疗的年龄相关特征。

Age-related features of lung cancer treatment using reprogrammed CD8 positive T cells in mice subjected to injection of Lewis lung carcinoma cells.

作者信息

Skurikhin Evgenii, Zhukova Mariia, Ermakova Natalia, Pan Edgar, Widera Darius, Sandrikina Lubov, Kogai Lena, Kushlinskii Nikolai, Kubatiev Aslan, Morozov Sergey, Dygai Alexander

机构信息

Institute of General Pathology and Pathophysiology, Moscow, Russia.

Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, Whiteknights Campus, Reading, UK.

出版信息

Thorac Cancer. 2024 Oct;15(28):2000-2020. doi: 10.1111/1759-7714.15426. Epub 2024 Aug 22.

Abstract

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.

摘要

背景

了解癌症发生的年龄相关特征以及细胞免疫的重要性对于为特定患者群体开发有效的抗肿瘤治疗方法至关重要。

方法

在本研究中,我们检测了“年轻”(8 - 10周)和“老年”(80 - 82周)C57BL/6雄性小鼠体内不同群体的癌症干细胞(CSCs)和循环肿瘤细胞(CTCs)。我们使用Lewis肺癌(LLC)原位模型来评估通过重编程CD8阳性T细胞(rCD8 + T细胞)对来自两个不同年龄小鼠的肺癌进行细胞治疗的有效性。

结果

研究结果表明,肿瘤随年龄进展主要是由于T细胞向肺部募集受损所致。此外,与老年小鼠相比,年轻小鼠体内的CTCs和CSCs数量较少。发现rCD8 + T细胞对老年小鼠的抗肿瘤作用不如对年轻小鼠,这可归因于该疗法对特定CSCs群体的影响较小。

结论

这些结果为使用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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4923/11444928/cb554fe02407/TCA-15-2000-g004.jpg

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