Supporting data for “SOX4 is a master regulator of initiation, progression and immune evasion in Nasopharyngeal Carcinoma via disruption of zinc homeostasis”

Based on single-cell RNA sequencing (scRNA-seq) analysis and bulk transcriptome data validation, we observed specifically and significantly high expression levels of SRY-Box transcription factor 4 (SOX4), an essential developmental transcription factor, in NPC cells compared to infiltrating immune and stromal cells. In our study, we found that the upregulation of SOX4 contributed to tumor growth, distant metastasis, and stemness maintenance. More interestingly, we noticed NPC cells could affect infiltrated CD8+ T cell function via competitive zinc deprivation. During this process, the overexpressed SOX4 promoted the upregulation of downstream target SLC39A14 (ZIP14), which is the zinc transporter protein, to uptake excessive zinc from the extracellular microenvironment, as a result, leading to zinc competitive deprivation in infiltrated T cells. T-cell zinc competitive deprivation inhibited TCR signaling, impeded T-cell activation, and caused CD8+ T cytotoxicity failure, ultimately resulting in NPC immune evasion. This study first demonstrated that the SOX4-ZIP14-zinc axis played a crucial role in both the induction of tumor progression and the suppression of the immune response in NPC.