GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329266/primaryOK200TranscriptomicsMus musculusExpression profiling by arrayhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329266GEOGSEfalseNanostring nCounter Mouse PanCancer Immune Profiling analysis of murine tumor tissuesThe immunosuppressive tumor microenvironment (TME) contributes to resistance against checkpoint inhibitors. However, the precise factors that shape the immune contexture of the TME remain elusive. Here, we report that Single-Stranded DNA Binding Protein 4 (SSBP4), a previously uncharacterized protein, suppresses intratumoral T-cell activation by promoting excessive cholesteryl ester production in tumor cells. Overexpression of SSBP4 in tumor cells decreased T-cell infiltration and accelerated tumor growth in murine syngeneic tumor models. Conversely, genetic ablation of SSBP4 in tumor cells enhanced T-cell infiltration and inhibited tumor growth in a CD8+ T cell–-dependent manner. Mechanistically, SSBP4 upregulated cholesterol synthesis genes, leading to increased production of cholesterol and cholesteryl esters in tumor cells, which directly suppressed CD8+ T-cell activation and function. Furthermore, SSBP4 abrogation significantly improved the efficacy of anti-PD-1 treatment. Thus, in this study, we have identified SSBP4 as a cancer cell–intrinsic regulator of cholesterol metabolism that contributes to tumor immune evasion. Immune-related gene expression was quantified using the Nanostring Mouse PanCancer Immune Profiling panel. Total RNA was isolated from the C57BL/6 SSBP4-wildtype or knockout B16F10 tumors on Day 15 post tumor inoculation. RNA was hybridized, scanned on a Nanostring Digital Analyzer, and raw RCC files were generated. Raw count data were processed and normalized in nSolver or ROSALIND software for downstream immune transcriptome profiling.2026/04/30GSE329266GSM9700411GSM9700410GSM9700413GSM9700412GSM9700404GSM9700406GSM9700405GSM9700408GSM9700407GSM970040925652329266Mus musculus