Overview

• Combining the macropinocytosis inhibitor EIPA with anti-PD-1 antibodies significantly suppressed tumor metastasis and extended survival in PDAC-bearing mice.
• Pre-treating tumors with EIPA before administering gemcitabine chemotherapy led to synergistic reductions in tumor growth and lung micrometastases.
• EIPA-induced glutamine stress in cancer-associated fibroblasts triggered a shift from collagen-producing myofibroblasts to inflammatory CAFs.
• Macropinocytosis blockade reduced stromal fibrosis, widened blood vessels and increased CD4+ and CD8+ T cell infiltration into pancreatic tumors.
• Researchers propose that targeting nutrient scavenging in the tumor microenvironment could form the basis for new combination therapies against glutamine-dependent cancers.