RBM10 inhibits pancreatic cancer development by suppressing immune escape through PD-1 expression

TL;DR

RBM10 helps fight pancreatic cancer by boosting immune response through PD-1 regulation in natural killer cells.

Contribution

RBM10's role in suppressing immune escape via PD-1 in NK cells is newly identified in pancreatic cancer.

Findings

RBM10 levels are lower in pancreatic cancerous tissues compared to non-cancerous tissues.

RBM10 deficiency increases PD-1 expression in NK cells, reducing their tumor-killing ability.

High RBM10 expression correlates with better prognosis in pancreatic cancer patients.

Abstract

RNA-binding motif protein-10 (RBM10) plays a role in pancreatic adenocarcinoma (PAAD), though its precise underlying mechanism remains unclear. The current study investigates the role of RBM10 in pancreatic cancer progression and immune regulation.

RBM10 expression in pancreatic tissues from PAAD patient was assessed using Western blotting, RT-qPCR, and immunohistochemistry, revealing lower levels in pancreatic cancerous tissues compared to adjacent non-cancerous tissues. This finding aligns with in vitro experiments where RBM10 knockdown in pancreatic cancer cells enhanced colony formation, migration, and proliferation, which correlated with increased P-JAK1, P‑JAK2, and P-STAT3 levels. Bioinformatics identified RBM10-related pathways and immune changes. Moreover, RBM10 deficiency in cancer cells increased PD-1 expression in natural killer cells in vitro, reducing their tumour-killing ability. However, treatment with the JAK pathway inhibitor AZD1480 restored NK cell cytotoxicity against cancer cells.

Finally, high RBM10 expression was associated with a favourable prognosis in pancreatic cancer patients, suggesting that RBM10 inhibits pancreatic cancer progression by suppressing tumour immune escape through JAK-STAT-mediated regulation of PD-1 expression in NK cells. This finding offers potential for the development of novel precision-targeted therapies in the management of pancreatic cancer.

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