CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tissue-resident memory CD103+CD8+ T cells in colorectal cancer: its implication as a prognostic and predictive liver metastasis biomarker.
Tissue-resident memory CD103+CD8+ T cells in colorectal cancer: its implication as a prognostic and predictive liver metastasis biomarker.
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我们证明 CD103⁺CD8⁺ TRMs 具有临床应用潜力,并为联合抗肿瘤治疗策略提供了新思路,例如抗肿瘤血管生成治疗和 CAR-T 联合免疫治疗。
组织驻留记忆CD103阳性CD8阳性T细胞是抗肿瘤免疫的重要组成部分,但其在结直肠癌中的意义尚不明确。本研究结合临床样本和小鼠模型评估其作用。患者肿瘤中该细胞浸润较高与较早临床分期、VEGF阴性及较好预后相关,并可能预测是否发生肝转移。抗血管生成治疗可增加其肿瘤浸润并增强干扰素γ分泌,从而提高抗肿瘤效果。与外周血CD8阳性T细胞相比,回输组织驻留记忆细胞可进一步促进CD8阳性T细胞浸润肿瘤,增强干扰素γ分泌并改善抗肿瘤作用。结果提示该细胞具有临床应用潜力,并为抗血管生成与CAR-T 联合等抗肿瘤策略提供新思路。
Tissue-resident memory CD103+CD8+ T cells (CD103+CD8+ TRMs) are important components of anti-tumor immunity. However, the significance of CD103+CD8+ TRMs in colorectal cancer (CRC) and their advantages remain unclear.
Clinical data and specimens were used to evaluate the significance of CD103+CD8+ TRMs in CRC. A mouse subcutaneous tumorigenesis model and colony-formation assay were conducted to evaluate the anti-tumor effects of CD103+CD8+ TRMs. Finally, the infiltration density and function of CD103+CD8+ TRMs in the tumors were evaluated using flow cytometry.
In this study, we showed that highly infiltrated CD103+CD8+ TRMs were associated with earlier clinical stage and negative VEGF expression in CRC patients and predicted a favorable prognosis for CRC/CRC liver metastases patients. Interestingly, we also found that CD103+CD8+ TRMs may have predictive potential for whether CRC develops liver metastasis in CRC. In addition, we found a positive correlation between the ratio of the number of -SMA+ vessels to the sum of the number of -SMA+ and CD31+ vessels in CRC, and the infiltration level of CD103+CD8+ TRMs. In addition, anti-angiogenic therapy promoted infiltration of CD103+CD8+ TRMs and enhanced their ability to secrete interferon (IFN)- , thus further improving the anti-tumor effect. Moreover, in vivo experiments showed that compared with peripheral blood CD8+ T cells, CD103+CD8+ TRMs infused back into the body could also further promote CD8+ T cells to infiltrate the tumor, and they had a stronger ability to secrete IFN- , which resulted in better anti-tumor effects.
We demonstrated that CD103+CD8+ TRMs have the potential for clinical applications and provide new ideas for combined anti-tumor therapeutic strategies, such as anti-tumor angiogenesis therapy and CAR-T combined immunotherapy.
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