我科学家提出肿瘤免疫治疗新策略

Core Insights - The research team from Westlake University has revealed a new mechanism by which tumor microenvironments inhibit dendritic cell migration in tissue interstices, proposing a novel tumor immunotherapy strategy using the PDE5 inhibitor sildenafil to restore dendritic cell function [1][2] Group 1: Research Findings - Dendritic cells, acting as "informants" of the immune system, are responsible for conveying tumor antigen information to draining lymph nodes, activating T cells to attack [1] - Analysis of samples from patients with pancreatic, breast, and colorectal cancers showed a significant reduction in mature dendritic cells in draining lymph nodes as tumor progression occurred [1] - The research identified PDE5 as the most significant regulatory factor affecting dendritic cell entry into draining lymph nodes, with experiments confirming that knocking out PDE5 significantly promotes dendritic cell migration [1] Group 2: Mechanism of Action - PDE5 functions to degrade cyclic guanosine monophosphate (cGMP), which promotes cell migration; the study found that low levels of nitric oxide in the tumor microenvironment lead to insufficient cGMP synthesis, reducing dendritic cell migration and weakening tumor immune response [2] - The PDE5 inhibitor sildenafil was found to significantly enhance dendritic cell migration and boost tumor-specific T cell responses, controlling tumor growth [2] - This research is the first to uncover the immunological mechanism of sildenafil, providing a new theoretical basis for its use as an immunotherapy drug [2]