The ImmunoVerse™ From KRAS to CD40: Advancing Pancreatic Cancer Immunotherapy, ft. Dr. Robert Vonderheide
Nov 21, 2025
Dr. Robert Vonderheide, a leading physician-scientist and director at the Abramson Cancer Center, dives into the complexities of pancreatic cancer and immunotherapy. He discusses his evolving perspective on cancer treatment, emphasizing the unique challenges of pancreatic tumors, driven by the KRAS oncogene. Vonderheide explores innovative strategies that combine KRAS inhibitors with immunotherapies like CD40 agonists to enhance immune responses. He also highlights the critical need for early detection and the importance of fostering mentorship in the field.
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Why Pancreatic Cancer Evades Immunity
- Pancreatic cancer lacks the high mutation burden that makes melanoma immunogenic.
- Its deep location and dense stromal scar tissue cause immune cells to 'drive right by' and ignore the tumor.
Why Vonderheide Chose Pancreatic Cancer
- Dr. Robert Vonderheide focused on pancreatic cancer after caring for many patients and seeing the urgent need.
- He realized melanoma strategies couldn't be copy-pasted and returned to mechanistic lab work to understand pancreatic biology.
KRAS Shapes An Immunosuppressive Microenvironment
- KRAS-driven pancreatic tumors orchestrate an immunosuppressive microenvironment from the earliest stages.
- That environment includes myeloid suppressor cells, macrophages, regulatory T cells, and dense connective tissue that block T-cell infiltration.