GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329267/primaryOK200TranscriptomicsMus musculusExpression profiling by arrayhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329267GEOGSEfalseNanostring nCounter Myeloid Innate Immunity analysis of CD8 T cells cultured with conditioned mediaThe 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 nCounter Myeloid Innate Immunity Panel. Total RNA was isolated from splenic CD8 T cells of C57BL/6 mice, where were cultured with conditioned media from SSBP4-wildtype or knockout B16F10 tumor cells. RNA was extracted from CD8 T cells, hybridized, scanned on a Nanostring Digital Analyzer, and raw RCC files were generated. Raw count data were processed and normalized in nSolver software for downstream immune transcriptome profiling.2026/04/30GSE329267GSM9700420GSM9700421GSM9700415GSM9700414GSM9700417GSM9700416GSM9700419GSM970041825266329267Mus musculus