ITPRIPL1, also known as CD3L1 (CD3ε ligand 1), is a single-pass type I membrane protein that functions as an inhibitory ligand of CD3ε [1,3]. It plays a crucial role in the immune response, especially in the regulation of T-cell activation. By binding to CD3ε on T-cells, it impacts the calcium influx and ZAP70 phosphorylation, thereby influencing the initial T-cell activation process [1]. This interaction is involved in the tumor immune evasion pathway, making it a molecule of great biological importance in the context of cancer immunology.

Treatment with a neutralizing antibody against ITPRIPL1 in mouse models across various solid tumor types restrained tumor growth and promoted T-cell infiltration [1]. In non-small cell lung cancer (NSCLC) patient tissue samples, ITPRIPL1 is widely overexpressed and positively correlates with tumor stages, while negatively correlating with CD8 staining, indicating poorer immune infiltration and clinical prognosis [2]. A comprehensive pan-cancer analysis showed that ITPRIPL1 expression varies significantly across different cancer types, and in some cancers like breast cancer (BRCA), high expression is associated with a better prognosis. Also, its expression highly correlates with tumor-infiltrating immune cells, immune checkpoint genes, tumor mutation burden (TMB), and tumor microsatellite instability (MSI) in multiple cancer types [3].

In conclusion, ITPRIPL1 is a key molecule in regulating T-cell activation and tumor immune evasion. The findings from mouse models and human cancer tissue studies suggest its potential as a therapeutic target for multiple tumor types. Its expression patterns and associations with immune-related factors across different cancers highlight its importance in understanding cancer immunology and developing new cancer treatment strategies.