Dual Roles of EZH2 in Tumor Proliferation and Immune Evasion in Lung Squamous Cell Carcinoma: A Pathway to Novel Immunotherapeutic Approaches.

Abstract

Abstract: Lung squamous cell carcinoma (LUSC) remains a major clinical challenge due to its aggressive nature and poor prognosis. Enhancer of zeste homolog 2 (EZH2), a key epigenetic regulator within the polycomb repressive complex 2 (PRC2), has emerged as a critical player in cancer progression. This study investigates the dual role of EZH2 in driving tumor proliferation and modulating the immune microenvironment in LUSC. Bioinformatics analysis revealed significant upregulation of EZH2 in LUSC tissues compared with normal counterparts, with high EZH2 expression correlating with improved overall survival in early-stage patients. Functional assays in EZH2 knockout LUSC cell lines demonstrated reduced tumor cell proliferation, migration, and invasion alongside enhanced apoptosis and cell cycle arrest. Furthermore, in vivo studies using an EZH2 knockout mouse model showed decreased tumor growth and increased immune cell infiltration, including CD8+ T cells, macrophages, and neutrophils. These findings highlight the pivotal role of EZH2 in promoting tumor progression and orchestrating immune evasion mechanisms in LUSC. Given its multifaceted influence on tumor biology and the immune landscape, EZH2 represents a promising therapeutic target for improving outcomes in LUSC patients. Future studies should explore the therapeutic potential of targeting EZH2 to enhance immune responses and overcome resistance to current treatments.