RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Expressions of CXCR3 and PD-1 on T cells and their clinical relevance in colorectal cancer.
Expressions of CXCR3 and PD-1 on T cells and their clinical relevance in colorectal cancer.
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肿瘤浸润性 T 淋巴细胞上 CXCR3 和 PD-1 的表达与 CRC 的发生和转移相关,为探索 CRC 的发病机制和开发肿瘤免疫治疗新策略提供了线索。
以程序性死亡受体1(PD-1)单克隆抗体为代表的免疫治疗临床应用已改变结直肠癌(CRC)的治疗格局,而肿瘤浸润性T淋巴细胞对于CRC的抗PD-1治疗至关重要。然而,关于T淋巴细胞上CXCR3表达与CRC临床特征之间关系的研究较少。在本研究中,我们分析了健康供者(HDs)和CRC患者CD8+和CD4+T淋巴细胞中CXCR3和PD-1的表达水平。
我们采用流式细胞术检测了健康供者外周血以及CRC患者外周血、肿瘤组织和癌旁组织中T淋巴细胞上CXCR3和PD-1的表达。我们还采用t检验分析了T淋巴细胞上CXCR3和PD-1的表达与CRC病理特征之间的关系。
在CRC患者中,肿瘤浸润性T淋巴细胞上CXCR3的表达低于癌旁组织和PB,而PD-1的表达则高于癌旁组织和PB。在伴有淋巴结转移的CRC患者中,肿瘤浸润性CD8+和CD4+T淋巴细胞上CXCR3+PD-1+的表达水平高于无淋巴结转移的患者。CXCR3+PD-1+的表达水平因原发肿瘤部位的不同而存在差异。
Clinical application of immunotherapy represented by Programmed Death-1 (PD-1) monoclonal antibody has changed the treatment paradigm for colorectal cancer (CRC), and tumor-infiltrating T lymphocytes are critical for anti-PD-1 therapy in CRC. However, there are few studies on the relationship between the expression CXCR3 on T lymphocytes and the clinical aspects of CRC. In this study, we analyzed the expression levels of CXCR3 and PD-1 in CD8 + and CD4 + T lymphocytes in healthy donors (HDs) and patients with CRC.
We detected the expressions of CXCR3 and PD-1 on T lymphocytes in peripheral blood of healthy donors as well as peripheral blood, tumor tissue and para-cancerous tissues of patients with CRC using flow cytometry. We also analyzed the relationship between the expressions of CXCR3 and PD-1 on T lymphocytes and the pathological characteristics of CRC using t test.
Expression of CXCR3 on tumor-infiltrating T lymphocytes was lower, whereas the expression of PD-1 was higher than that on para-cancerous tissues and PB in patients with CRC. In patients with lymph node metastasis of CRC, the expressions levels of CXCR3 + PD-1 + on tumor-infiltrating CD8 + and CD4 + T lymphocytes were higher than those in patients without lymph node metastasis. The levels of CXCR3 + PD-1 + expressions differed depending on the primary tumor site.
Expressions of CXCR3 and PD-1 on tumor-infiltrating T lymphocytes are related to the development of CRC and metastasis, providing clues for exploring the pathogenesis of CRC and developing new strategies for tumor immunotherapy.
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