Alterations in NK cell subsets and the regulatory role of JAB1 in nasopharyngeal carcinoma with implications for tumor immunity and biomarker development

Abstract

This study investigates changes in NK cell subsets in the blood of NPC patients and explores JAB1’s role in shaping the tumor immune environment. We performed RNA sequencing analyses on NPC PBMCs and tissue samples to identify genes associated with JAB1. Dimensionality reduction and clustering analyses were conducted on paired single-cell RNA sequencing data to explore differences in NK cell subsets. Functional assays assessed the roles of these subsets in various immune environments. Flow cytometry characterised NK cell subsets and cytokine profiles. A humanised immune system mouse model with NPC xenografts supported our findings. Higher levels of CD16 + CD57 + NK cells in blood correlated with better patient outcomes, while increased CD16- NK cells indicated worse prognoses. JAB1 enhanced NK cell cytotoxicity, indicating its role in immune regulation. NK subsets showed distinct distributions: CD16hiCD57- and CD16hiCD57+ cells were mainly in blood, while CD16loCD57- cells accumulated in tumors. Functional tests revealed some subsets promoted tumor growth while others suppressed it. Expression of JAB1 and CD107a in NK cells demonstrated superior diagnostic and prognostic value compared to traditional tumor markers like SCC and CEA. This study identifies key roles of NK cell subsets and JAB1 in NPC immunity, offering insights for biomarker and immunotherapy target development.