標靶 COX-2/PGE₂ 軸以增強針對膠質母細胞瘤的 NK 細胞和 T 細胞免疫療法

Glioblastoma (GBM) remains one of the most aggressive and lethal brain cancers, with a median survival rate of approximately 15 months despite multimodal standard care. The primary obstacle to successful treatment is the highly immunosuppressive Tumor Microenvironment (TME), which actively dampens the efficacy of emerging Natural Killer (NK) and T cell immunotherapies. This thesis investigates the COX-2/PGE₂ signaling axis as a central mechanism of immune evasion and evaluates the potential of targeting this pathway to enhance cellular immunotherapy. Utilizing a dual-methodological approach, this research combines original in vitro experiments with a comprehensive literature review of preclinical studies and clinical trials from 2015 to 2025. Experimental assays involved co-culturing U87MG-Luciferase GBM cells with NK92 effector cells under treatment with various prostaglandins. Results demonstrate that Prostaglandin E2 (PGE₂ ) significantly suppresses NK cell activity, leading to a 4-5-fold reduction in cytotoxicity, impaired proliferation. The systematic review highlights that while early-phase trials of Chimeric Antigen Receptor (CAR) T and CAR-NK Cell therapies (targeting antigens like EGFRvIII and IL13Ra2) have confirmed safety, their therapeutic efficacy remains limited by PGE₂ -mediated barriers, including metabolic reprogramming, T cell exhaustion, and restricted infiltration. The findings conclude that the COX-2/PGE₂ axis is a critical driver of immunotherapy failure in GBM. Integrating PGE₂ inhibitors or E-type Prostanoid receptor antagonists as adjuvants to adoptive cellular therapies offers a promising translational strategy to overcome TME-induced suppression and improve clinical outcomes for GBM patients.