Researchers have identified a molecular pathway in cancer-associated fibroblasts that drives immune evasion in pancreatic ductal adenocarcinoma, according to a peer-reviewed study published in Nature Communications on August 7, 2026.
The findings show that Lin28b-positive cancer-associated fibroblasts establish an immunologically cold tumor microenvironment. At the molecular level, Lin28b binds directly to STING mRNA and promotes its degradation. This process suppresses STING expression and shuts down downstream type I interferon signaling, preventing an effective anti-tumor immune response.
Eliminating Lin28b in these fibroblasts alters the cellular environment. Loss of Lin28b activates the cGAS-STING-interferon signaling cascade, which enhances dendritic cell antigen presentation and increases the cytotoxic function of CD8-positive T cells. Genetic inhibition of Lin28b in cancer-associated fibroblasts improved sensitivity to anti-PD-L1 immune checkpoint blockade therapy, identifying a direct strategy for addressing intrinsic immunotherapy resistance in pancreatic ductal adenocarcinoma.
Minghe Fan, Ziyang Zhang, and Wei Xu contributed equally to the study alongside co-authors from Peking University Health Science Center, Peking University Cancer Hospital, and Shenzhen University Medical School. Dr. Haoqiang Ying provided 15376T cells for the research, and analysis was supported by the High-performance Computing Platform of Peking University under funding from the National Key R&D Program of China and the National Natural Science Foundation of China.
