藤皮卷翅苣苔提高肿瘤浸润的T淋巴细胞对结直肠癌的免疫应答。
Marsdenia tenacissima enhances immune response of tumor infiltrating T lymphocytes to colorectal cancer.
发表日期:2023
作者:
Ben Yi, Shuai Zhang, Suying Yan, Yanfei Liu, Zhiqiang Feng, Tianhao Chu, Jun Liu, Wei Wang, Jun Xue, Chunze Zhang, Yijia Wang
来源:
Frontiers in Immunology
摘要:
肿瘤微环境中的肿瘤浸润性T淋巴细胞是影响预后和化疗效果的关键因素。作为一种中草药,天仙藤提取物(MTE)在中国被广泛用于治疗癌症。它对肿瘤相关巨噬细胞的免疫调控作用已经被广为人知,但它是否调节肿瘤浸润性T细胞的功能尚不清楚。我们从接受MTE治疗的结直肠癌患者中收集了17个肿瘤样本,其中13个显示出CD3+/CD8+肿瘤浸润性T细胞的上调。进一步进行了体外和体内实验,以研究MTE对肿瘤浸润性T细胞和肿瘤免疫逃避的调节作用。在单独和共培养条件下,MTE抑制了结直肠癌细胞系HCT116和LoVo中TGF-β1和PD-L1的表达。在Jurkat细胞中,MTE抑制了FOXP3和IL-10的表达,增加了IL-2的表达,但对PD-1的表达没有影响。这些发现在体外及皮下和结肠炎相关的结直肠癌小鼠模型中得到了证实。MTE还增加了CD3+/CD8+肿瘤浸润性T细胞的密度,并在这两个肿瘤小鼠模型中展示了明显的抑制肿瘤效应。我们的研究结果表明,MTE抑制了癌细胞的免疫逃避,这是导致T淋巴细胞免疫反应增加的促进因素。版权所有©2023 Yi, Zhang, Yan, Liu, Feng, Chu, Liu, Wang, Xue, Zhang和Wang。
Tumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear.We collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors.Under single and co-culture conditions, MTE inhibited TGF-β1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models.Our findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes.Copyright © 2023 Yi, Zhang, Yan, Liu, Feng, Chu, Liu, Wang, Xue, Zhang and Wang.