Facilitation of natural killer T-cell cytotoxic activity in uterine sarcoma via the axis.

BACKGROUND

Uterine sarcoma constitutes approximately 3-7% of all uterine cancers, with adenosarcoma and leiomyosarcoma being the major subtypes. This neoplasm is characterized by poor clinical outcomes, with frequent recurrence and metastasis, underscoring the urgent need for early detection strategies. Cyclin-dependent kinase regulatory subunit 2 () is markedly overexpressed in uterine sarcoma. Preliminary data suggest that overexpression correlates with advanced tumor staging, yet its mechanistic link to immune evasion via natural killer T (NKT)-cell regulation remains unexplored. This study aimed to explore how regulates the immune response in uterine sarcoma.

METHODS

Through the integration of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, a systematic analysis was conducted on the correlation between expression levels, tumor prognostic staging, and immune cell infiltration. Stable -knockdown cell lines were constructed, and the expression changes of were detected via quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot techniques. Through colony formation assays, TUNEL staining, invasion and migration assays, and Western blot analysis, the mechanism related to the regulatory effect of on the malignant progression of uterine sarcoma cells was clarified in depth. Additionally, the specific mechanism by which regulates NKT cell activity was verified at the tissue level via multiplex immunofluorescence.

RESULTS

In uterine sarcoma, expression was found to be significantly upregulated and closely associated with poor prognosis, advanced tumor stage, and a distinct negative correlation with NKT cell activity. experiments indicated that knockdown of significantly inhibited the proliferation, migration, and invasion of sarcoma cells and promoted apoptosis. Mechanistically, activated the signaling, reduced major histocompatibility complex (MHC) class I chain-related protein A () expression, and inhibited NKT cell activity, resulting in immune escape, which was effectively mitigated by inhibitors.

CONCLUSIONS

The findings suggest that can serve as a valuable biomarker and an effective target for the prevention and screening of uterine sarcoma and can modify the antitumor immune response in uterine sarcoma.