Liang Rongpu, Liu Liting, Ding Dongbing, Li Yiquan, Ren Jiannan, Wei Bo
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People's Republic of China.
Department of Gastrointestinal Surgery, Lingnan Hospital, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
Cancer Immunol Immunother. 2025 Feb 1;74(3):94. doi: 10.1007/s00262-025-03947-y.
CD155 is a crucial factor in the regulation of T cell function and contributes to immune escape. CD155 upregulation has been found in several types of cancer. However, the mechanism by which CD155 regulates CD8 T cell function in colorectal cancer remains unclear. Here we investigated the role and mechanism of CD155 in the regulation of CD8 T cell function.
We studied the expression of CD155 in colorectal cancer tissues through western blot, immunohistochemistry, and the TCGA database. We verified the effects of CD155 on the functions of colorectal cancer cells and CD8 T cells through in vitro experiments. We demonstrated that CD155 affects CD8 T cell migration and thus promotes tumor growth in a mouse subcutaneous tumor model. We then tested the changes in the PI3K/AKT/NF-κB pathway in CD8 T cells by flow cytometry.
We demonstrated that stable CD155 expression was negatively correlated with prognosis in colorectal cancer patients. In vitro experiments confirmed that CD155 does not affect tumor cell proliferation, migration, or invasion. We also revealed that CD155 downregulated the function and migration of CD8 T cells in vivo and in vitro. Furthermore, CD155 might regulate CD8 T cells function via the PI3K/AKT/NF-κB pathway.
This study revealed that CD155 can promote the progression of colorectal cancer by regulating the PI3K / AKT-NF-κB pathway to promote the depletion of CD8 T cells and reduce their migration to the tumor microenvironment. CD155 may become an important prognostic biomarker and an effective target for colorectal cancer immunotherapy.
CD155是调节T细胞功能的关键因素，有助于免疫逃逸。在几种类型的癌症中均发现CD155上调。然而，CD155在结直肠癌中调节CD8 T细胞功能的机制仍不清楚。在此，我们研究了CD155在调节CD8 T细胞功能中的作用和机制。
我们通过蛋白质印迹法、免疫组织化学和TCGA数据库研究了结直肠癌组织中CD155的表达。我们通过体外实验验证了CD155对结直肠癌细胞和CD8 T细胞功能的影响。我们证明CD155影响CD8 T细胞迁移，从而在小鼠皮下肿瘤模型中促进肿瘤生长。然后，我们通过流式细胞术检测了CD8 T细胞中PI3K/AKT/NF-κB信号通路的变化。
我们证明，CD155的稳定表达与结直肠癌患者的预后呈负相关。体外实验证实，CD155不影响肿瘤细胞的增殖、迁移或侵袭。我们还发现，CD155在体内和体外均下调了CD8 T细胞的功能和迁移。此外，CD155可能通过PI3K/AKT/NF-κB信号通路调节CD8 T细胞功能。
本研究表明，CD155可通过调节PI3K / AKT-NF-κB信号通路促进CD8 T细胞耗竭并减少其向肿瘤微环境的迁移，从而促进结直肠癌进展。CD155可能成为结直肠癌重要的预后生物标志物和有效的免疫治疗靶点。
