Stromnes Lab Identifies New Strategy to Overcome Immunotherapy Resistance in Pancreatic Cancer

Congratulations to the Stromnes Lab on the publication of their latest research in Science Immunology!

In their paper, "Treg cells promote immunotherapy-induced immune evasion by restraining CD4 T cell control of MHC-I–deficient metastatic pancreatic cancer," first author Zoe C. Schmiechen and colleagues uncover a key mechanism by which pancreatic ductal adenocarcinoma (PDA) escapes immune attack following immunotherapy.

Pancreatic cancer remains one of the most challenging cancers to treat, with many tumors developing resistance to immune checkpoint therapies. The researchers found that after PD-L1 blockade, tumor cells can evade immune detection by silencing Tap1, a gene required for MHC-I antigen presentation. This loss of MHC-I allows metastatic tumor cells to escape recognition by the immune system. The study further demonstrates that regulatory T cells (Tregs) suppress the activity of CD4 T cells that would otherwise eliminate these immune-evasive tumor cells.

Importantly, the team showed that restoring MHC-I expression, either genetically or pharmacologically, made treatment-resistant pancreatic tumors responsive to CTLA-4 blockade. Combining MHC-I restoration with anti-CTLA-4 therapy enhanced anti-tumor immunity, reduced metastasis, and prolonged survival in preclinical models. These findings highlight how correcting defects in antigen presentation may improve the effectiveness of immunotherapy for pancreatic cancer.

"This work demonstrates that pancreatic cancer can evade immune surveillance through loss of MHC-I expression and the suppressive activity of regulatory T cells," said senior author Dr. Ingunn Stromnes. "By restoring antigen presentation, we were able to re-sensitize treatment-resistant tumors to immunotherapy, providing a promising strategy for overcoming immune resistance."

The study was led by members of the Stromnes Lab at the University of Minnesota Center for Immunology and represents an important advance in understanding the mechanisms of immunotherapy resistance in metastatic pancreatic cancer.

Publication

Schmiechen ZC, Cruz-Hinojoza E, Hilk AL, et al. Treg cells promote immunotherapy-induced immune evasion by restraining CD4 T cell control of MHC-I–deficient metastatic pancreatic cancer. Science Immunology. 2026;11(120). doi:10.1126/sciimmunol.adz4302 

Read the full paper: https://www.science.org/doi/10.1126/sciimmunol.adz4302