通过蛋白精氨酸甲基转移酶 5 (PRMT5)/CXCL10 轴增强 CD8(+) T 细胞浸润可限制宫颈癌进展

PRMT5, a type II methyltransferase catalyzing symmetric dimethylation of arginine residues, has emerged as a promising therapeutic target in various cancers.

However, the precise mechanism by which PRMT5 mediated the tumor immune microenvironment, particularly CD8 + T cell recruitment in cervical cancer remains elusive. Analysis of data from The Cancer Genome Atlas (TCGA) revealed elevated PRMT5 mRNA levels in cervical cancer tissues, which correlated with reduced immune cell infiltration and poorer patient prognosis.

To further investigate the role of PRMT5 in tumor development, a CD8 knockout (KO) mouse tumor model was utilized. Significant inhibition of tumor growth was observed in cervical cancer using a mouse model lacking PRMT5.

Notably, this antitumor effect was attenuated in CD8 KO mice lacking functional CD8 + T cells.

Mechanistically, RNA sequencing (RNA-seq) analysis was conducted to explore how PRMT5 regulates immune cell recruitment. Disruption of PRMT5 was found to increase the secretion of chemokine CXCL10 by tumor cells. CXCL10 binds to its receptor CXCR3, thereby recruiting T cells to the tumor.

Furthermore, in CXCR3 KO mice, PRMT5 knockdown failed to enhance T cell infiltration into tumors.

These findings indicate that PRMT5 knockdown promotes CD8 + T cell recruitment to the tumor microenvironment via CXCL10 signaling.

Furthermore, the therapeutic efficacy of the selective PRMT5 inhibitor EPZ015666 was evaluated in a cervical cancer xenograft mouse model. Treatment with EPZ015666 effectively suppressed tumor growth. In summary, these findings elucidate a novel mechanism whereby PRMT5 depletion in cervical cancer cells triggers a CXCL10-mediated chemotactic response, enhancing CD8 + T cell infiltration and restricting tumor progression.

Thus, our study provides compelling evidence supporting the potential targeting of PRMT5 as a viable immunotherapeutic strategy for cervical cancer.