LFA-1 基因敲除抑制了肿瘤生长,并且与Treg细胞相关。
LFA-1 knockout inhibited the tumor growth and is correlated with treg cells.
发表日期:2023 Sep 18
作者:
Ting Niu, Zhengyang Li, Yiting Huang, Yuxiang Ye, Yilong Liu, Zhijin Ye, Lingbi Jiang, Xiaodong He, Lijing Wang, Jiangchao Li
来源:
Cellular & Molecular Immunology
摘要:
癌症免疫疗法已被证明在多种类型的癌症中具有临床疗效。淋巴细胞功能相关抗原1 (LFA-1)是一种整合素家族的黏附分子,主要表达在αβT细胞上。LFA-1与肿瘤免疫应答相关,但其具体机制仍未知。本研究采用LFA-1基因敲除(LFA-1-/-)小鼠携带皮下肿瘤和Apc Min/+;LFA-1-/-小鼠构建两种肿瘤模型,确认LFA-1敲除会抑制肿瘤生长。此外,研究还表明,在LFA-1-/-小鼠的脾脏、血液和肠系膜淋巴结中,调节性T细胞(Treg细胞)的数量减少,并且在Apc Min/+;LFA-1-/-小鼠的肠系膜淋巴结中,Treg细胞数量也减少,相比之下,Apc Min/+小鼠的Treg细胞数量较多。给予LFA-1抑制剂(BIRT377)的皮下肿瘤携带LFA-1+/+小鼠研究结果显示,肿瘤生长被抑制,Treg细胞数量减少。TIMER肿瘤数据库分析显示,LFA-1表达与Treg细胞和TNM分期呈正相关。综上所述,这表明LFA-1基因敲除可以抑制肿瘤生长并与Treg细胞相关。LFA-1可能是癌症免疫疗法的潜在靶点之一。视频摘要。© 2023. BioMed Central Ltd., 集Springer Nature之一。
Cancer immunotherapy has been proven to be clinically effective in multiple types of cancers. Lymphocyte function-associated antigen 1 (LFA-1), a member of the integrin family of adhesion molecules, is expressed mainly on αβ T cells. LFA-1 is associated with tumor immune responses, but its exact mechanism remains unknown. Here, two kinds of mice tumor model of LFA-1 knockout (LFA-1-/-) mice bearing subcutaneous tumor and Apc Min/+;LFA-1-/- mice were used to confirm that LFA-1 knockout resulted in inhibition of tumor growth. Furthermore, it also demonstrated that the numbers of regulatory T cells (Treg cells) in the spleen, blood, mesenteric lymph nodes were decreased in LFA-1-/- mice, and the numbers of Treg cells in mesenteric lymph nodes were also decreased in Apc Min/+;LFA-1-/- mice compared with Apc Min/+ mice. LFA-1 inhibitor (BIRT377) was administered to subcutaneous tumor-bearing LFA-1+/+ mice, and the results showed that the tumor growth was inhibited and the number of Treg cells was reduced. The analysis of TIMER tumor database indicated that LFA-1 expression is positively associated with Treg cells and TNM stage. Conclusively, this suggests that LFA-1 knockout would inhibit tumor growth and is correlated with Treg cells. LFA-1 may be one potential target for cancer immunotherapy. Video Abstract.© 2023. BioMed Central Ltd., part of Springer Nature.