Pancreatic ductal adenocarcinomas (PDACs) are classically immunologically cold tumors that have failed to demonstrate a significant response to immunotherapeutic strategies. This feature is attributed to both the immunosuppressive tumor microenvironment (TME) and limited immune cell access due to the surrounding stromal barrier, a histological hallmark of PDACs. In this issue of the JCI, Sharma et al. employ a broad glutamine antagonist, 6-diazo-5-oxo-l-norleucine (DON), to target a metabolic program that underlies both PDAC growth and hyaluronan production. Their findings describe an approach to converting the PDAC TME into a hot TME, thereby empowering immunotherapeutic strategies such as anti-PD1 therapy.

胰腺导管腺癌（PDAC）是经典的免疫学冷肿瘤，未能表现出对免疫治疗策略的显着反应。此功能归因于免疫抑制性肿瘤微环境（TME）和由于周围基质屏障（PDAC的组织学特征）而导致的免疫细胞通路受限。在JCI的这一期中，Sharma等人。采用了一种广泛的谷氨酰胺拮抗剂6-重氮基5-氧-l-正亮氨酸（DON）来靶向作为PDAC生长和透明质酸生产基础的代谢程序。他们的发现描述了一种将PDAC TME转换为热TME的方法，从而增强了免疫治疗策略，例如抗PD1治疗。