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结直肠癌中的组织驻留记忆 CD103+CD8+ T 细胞:作为预后及预测肝转移生物标志物的意义

英文原题:Tissue-resident memory CD103+CD8+ T cells in colorectal cancer: its implication as a prognostic and predictive liver metastasis biomarker.

查看英文原题

Tissue-resident memory CD103+CD8+ T cells in colorectal cancer: its implication as a prognostic and predictive liver metastasis biomarker.

PubMed 2024/07/02(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

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研究概要

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。

中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Liu S、Wang P、Wang P、Zhao Z、Zhang X、Pan Y、Pan J
第一作者单位
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.China
通讯作者单位
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China. panjh@jnu.edu.cn.China
期刊
Cancer immunology, immunotherapy : CII2024 Jul 2
原文标识
PubMed 38954030 · DOI 10.1007/s00262-024-03709-2