作者
Jashodeep Datta, Xizi Dai, Anna Bianchi, Iago De Castro Silva, Siddharth Mehra, Vanessa T Garrido, Purushottam Lamichhane, Samara P Singh, Zhiqun Zhou, Austin R Dosch, Fanuel Messaggio, Yuguang Ban, Oliver Umland, Peter J Hosein, Nagaraj S Nagathihalli, Nipun B Merchant
发表日期
2022/12/1
期刊
Gastroenterology
卷号
163
期号
6
页码范围
1593-1612
出版商
WB Saunders
简介
Background & Aims
We have shown that reciprocally activated rat sarcoma (RAS)/mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and Janus kinase/signal transducer and activator of transcription 3 (STAT3) pathways mediate therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC), while combined MEK and STAT3 inhibition (MEKi+STAT3i) overcomes such resistance and alters stromal architecture. We now determine whether MEKi+STAT3i reprograms the cancer-associated fibroblast (CAF) and immune microenvironment to overcome resistance to immune checkpoint inhibition in PDAC.
Methods
CAF and immune cell transcriptomes in MEKi (trametinib)+STAT3i (ruxolitinib)-treated vs vehicle-treated Ptf1aCre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) tumors were examined via single-cell RNA sequencing (scRNAseq). Clustered regularly interspaced short palindromic …
学术搜索中的文章
J Datta, X Dai, A Bianchi, IDC Silva, S Mehra… - Gastroenterology, 2022