Inositol 1,4,5-trisphosphate Receptor Interacting Protein-Like 1 (ITPRIPL1) is a transmembrane protein that is widely expressed in the testis and is associated with immune evasion mechanisms. ITPRIPL1 is specifically expressed in immune-privileged tissues, 'hot' tumors lacking PD-L1 expression, and tumors that do not respond to PD-1 blockade therapy. Experimental evidence has demonstrated that ITPRIPL1 can impair T cell function both in vitro and in vivo through interactions with CD3e, with a negative correlation observed between ITPRIPL1 expression levels in antigen-presenting cells and T cell cytotoxicity.
In the context of breast cancer, ITPRIPL1 has been identified as a hypermethylated, low-expression gene. Furthermore, using bioinformatics methods, ITPRIPL1 has been established as an independent biomarker for the prognosis of lung adenocarcinoma. Therefore, targeting the ITPRIPL1-CD3e axis, particularly in patients with PD-1/PD-L1 negative tumors, represents a promising therapeutic strategy to mitigate immune evasion.
ITPRIPL1 is also a significant biomarker for non-small cell lung cancer (NSCLC). The detection of ITPRIPL1 in tumors can aid in improved diagnosis, reveal the infiltration of CD8 positive T cells, monitor disease progression, and predict prognosis.
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