RPS4Y1 in immune modulation and progression of prostate cancer

The progression of prostate cancer (PCa) is commonly associated with the establishment of an immunosuppressive tumor microenvironment that enables immune evasion. Here, we identify ribosomal protein S4 Y-linked 1 ( RPS4Y1 ) as a candidate regulator of both tumor progression and immune modulation in PCa. RPS4Y1 is highly expressed in PCa tissues, and its downregulation significantly inhibits cancer cell proliferation, migration, and invasion. Transcriptomic profiling revealed a gene expression signature associated with immune responses following RPS4Y1 downregulation. This signature was recapitulated in the TCGA PCa cohort. Immune response scores were significantly higher in low RPS4Y1 expression tumors than in the high expression group. To examine the immune cell subpopulations associated with RPS4Y1 downregulation, we analyzed public single-cell RNA sequencing (scRNA-seq) datasets, which revealed reduced tumor cell abundance and increased cytotoxic immune cell populations in the RPS4Y1 -low group. Notably, NK cells were markedly expanded, driven by the CD56bright IL7R⁺ subset. Therefore, our study highlights the dual role of RPS4Y1 in tumor progression and immune modulation, suggesting its potential as a therapeutic target for reprogramming the immune microenvironment in PCa.