Institute of Basic Medical Sciences, School of Life Sciences and Biopharmaceuticals, Guangdong Pharmaceutical University, No. 280 Waihuan Rd. E, Higher Education Mega Center, 510006, Guangzhou, China.
Cell Commun Signal. 2023 Sep 18;21(1):233. doi: 10.1186/s12964-023-01238-6.
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 ;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 ;LFA-1 mice compared with Apc 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.
癌症免疫疗法已被证明在多种癌症中具有临床疗效。淋巴细胞功能相关抗原 1（LFA-1）是整合素家族黏附分子的成员，主要表达于αβ T 细胞。LFA-1 与肿瘤免疫反应有关，但确切机制尚不清楚。本研究构建了 LFA-1 敲除（LFA-1）小鼠的两种皮下肿瘤模型和 Apc ;LFA-1 小鼠，证实 LFA-1 敲除可抑制肿瘤生长。此外，还表明 LFA-1 敲除小鼠脾脏、血液和肠系膜淋巴结中的调节性 T 细胞（Treg 细胞）数量减少，与 Apc 小鼠相比，Apc ;LFA-1 小鼠肠系膜淋巴结中的 Treg 细胞数量也减少。给予 LFA-1 抑制剂（BIRT377）皮下荷瘤 LFA-1 小鼠，结果显示肿瘤生长受到抑制，Treg 细胞数量减少。TIMER 肿瘤数据库分析表明，LFA-1 表达与 Treg 细胞和 TNM 分期呈正相关。综上，LFA-1 敲除抑制肿瘤生长与 Treg 细胞相关，LFA-1 可能是癌症免疫治疗的一个潜在靶点。
