时间标签：数据日期 2026-11-03 · 生成时间 2026-11-03 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/31 – 2026/11/03 ｜ 情报发生日期 2026-11-03
研究问题
However, whether and how reduced sphingolipid synthesis remodels lipid raft abun- dance and function, and thereby modulates IFNγ-receptor localisation and signalling in PDAC, remains unclear.；Given that Il-1ra potently antagonises Il-1α-the key inducer of iCAFs in PDAC-we asked whether exogenous Il-1ra could block iCAF priming by KPCERT organoids.；To examine the cellular compartment associated with the interferon response in the mTORC2-deficient model, we performed spatial transcriptomic analysis of two KPCERT ; Rictor−/− tumors.
方法
Then, these mice were given tamoxifen and subjected to caerulein treatment for 2 consecutive days to induce acute pancreatitis.；The wild- type (WT, C57BL/6N) mice were obtained from Charles River Laboratory.；For all the experiments in this study, mice were housed under specific and opportunistic pathogen-free (SOPF) condition.
核心结论
Collectively, genetic inactivation of either mTOR complex delays PDAC progression, but only mTORC1 loss alters the tumour microenvironment, reducing desmoplasia and enhancing adaptive immune infiltration, via adaptive PI3K/Akt signalling hyperactiva- tion.；These data suggest that loss of mTORC1 activity in PDAC cells selectively impairs iCAF differentiation.；Collectively, these findings indicate that mTORC1 loss in PDAC cells elevates tumour-derived Il-1ra, thereby restraining Il-1-driven iCAF differentiation and attenuating iCAF-associated cytokine production.
局限
However, clinical use of mTOR inhibitors has shown limited efficacy due to rapid adaptive resistance.；However, CAF heterogeneity complicates selective targeting.
对本项目的价值
中等价值：属「营养感知—自噬—蛋白稳态轴」方向；肿瘤相关衰老机制（交叉参考）栏目可用作本项目文献库与综述素材。 ｜ 价值分 2.6/5（★★★☆☆）
全文来源
出版商/仓储 OA PDF（正文 54,515 字符，题名指纹 1.00，已过 DOI 逐字 + 题名指纹 + 正文长度三重归属校验）
原文题录
- 中文题名：双重抑制 mTORC1/2 与 Scd1 暴露胰腺癌的治疗脆弱性
- 英文标题：Dual mTORC1/2 and Scd1 inhibition uncovers a therapeutic vulnerability in pancreatic cancer.
- 期刊与标识：Oncogene · PMID 42966744 · DOI 10.1038/s41388-026-04026-x · EDAT 2026-11-01