外泌体 SNHG26 通过损害 NK 细胞介导舌癌中的免疫抑制

Cisplatin resistance in tongue squamous cell carcinoma (TSCC) correlates with poor prognosis, where natural killer (NK) cells in the tumor microenvironment (TME) play a crucial role.

This study investigated the mechanism by which exosomes from cisplatin-resistant TSCC cells suppress NK cell function.

We found that exosomal long non-coding RNA SNHG26, highly enriched in cisplatin-resistant TSCC cells and their exosomes, was transferred to NK cells. Within NK cells, SNHG26 acted as a scaffold promoting WWP2-mediated ubiquitination and degradation of the transcription factor SOX2, thereby inhibiting HLA-DRA transcription and subsequent IL-2/JAK-STAT5 signaling.

Concurrently, SNHG26 competitively bound miR-515-5p, relieving its suppression of TGFB1 mRNA and activating the TGF-β1/Smad2 pathway. These dual mechanisms significantly impaired NK cell proliferation, activation, and cytotoxicity. SNHG26 depletion reversed NK cell suppression and cisplatin resistance in vitro and in vivo.

Thus, our study identifies exosomal SNHG26 as a key mediator of cisplatin resistance and NK cell dysfunction in TSCC, suggesting its potential as a promising therapeutic target.