ITPRIPL1, also known as CD3L1 (CD3ε ligand 1), is a single-pass type I membrane protein that functions as an inhibitory ligand of CD3ε [1]. By binding to CD3ε on T cells, it significantly decreases calcium influx and ZAP70 phosphorylation, impeding the initial T cell activation during the "signal one" phase. This plays a crucial role in tumor immune evasion, making it potentially important in cancer-related immune regulation pathways [1].

Treatment with a neutralizing antibody against ITPRIPL1 in mouse models restrained tumor growth and promoted T cell infiltration across various solid tumor types, indicating that loss-of-function of ITPRIPL1 can enhance anti-tumor immune responses [1]. In NSCLC patients, ITPRIPL1 is widely overexpressed, positively correlated with tumor stages, and negatively correlated with CD8 + T cell infiltration, suggesting its role in suppressing anti-tumor immunity in this cancer type [2]. A pan-cancer analysis also showed that ITPRIPL1 expression varies across cancer types, is associated with immune infiltration, TMB, MSI, and has different prognostic values in different cancers [3].

In conclusion, ITPRIPL1 is a key molecule in the tumor immune evasion mechanism by impeding T cell activation. Studies using models like neutralizing antibody treatment in mouse models have revealed its significance in cancer. Its role in tumor development and immune regulation across multiple cancer types makes it a promising therapeutic target for human cancer [1,2,3].

References:

1. Deng, Shouyan, Zhang, Yibo, Wang, Huanbin, Quan, Yingfei, Xu, Jie. 2024. ITPRIPL1 binds CD3ε to impede T cell activation and enable tumor immune evasion. In Cell, 187, 2305-2323.e33. doi:10.1016/j.cell.2024.03.019. https://pubmed.ncbi.nlm.nih.gov/38614099/

2. Deng, Shouyan, Shi, Jiawei, Sun, Yufan, Li, Hai, Xu, Jie. 2023. Development of a monoclonal antibody to ITPRIPL1 for immunohistochemical diagnosis of non-small cell lung cancers: accuracy and correlation with CD8+ T cell infiltration. In Frontiers in cell and developmental biology, 11, 1297211. doi:10.3389/fcell.2023.1297211. https://pubmed.ncbi.nlm.nih.gov/38188019/

3. Duan, Wenyuan, Tian, Wen, Li, Zhongyi, Liu, Yunsong, Xu, Linping. 2024. A comprehensive pan-cancer analysis revealing the role of ITPRIPL1 as a prognostic and immunological biomarker. In Frontiers in molecular biosciences, 11, 1452290. doi:10.3389/fmolb.2024.1452290. https://pubmed.ncbi.nlm.nih.gov/39211744/