Researchers have identified a new potential immunotherapy target for pancreatic cancer, which has thus far been difficult to treat with immune checkpoint blockade drugs effective for other types of cancer. The findings were reported today in the Proceedings of the National Academy of Sciences.
The study was done by researchers at the University of Texas MD Anderson Cancer Center seeking to better understand infiltration of immune cells and expression of immunity-inhibiting checkpoints in pancreatic cancer. To do this, they compared pancreatic tumors to melanoma, the cancer that is most vulnerable to immune checkpoint blockade.
Comparing the two tumor types, the researchers found a high density of stroma, non-malignant supportive cells, in pancreatic cancer (comprising 70% of the tumor) and a lower density of stroma in melanoma (comprising 30% of the tumor). The distribution of the stroma and cancer cells also varied significantly. While pancreatic cancer and melanoma tumors had roughly the same number of T cell penetration, the T cells were mostly concentrated in the stroma of the pancreatic tumors.
In melanoma cells, the researchers found a heavier penetration of attacking immune T cells and higher levels of cells expressing inhibitory checkpoint molecules commonly used as treatment, including PD-1 and its activating ligand PD-L1. However, they found much higher expression of the immune checkpoint VISTA in pancreatic tumors.
VISTA is predominantly expressed on macrophages and is known to deactivate T cells. While the researchers found roughly equal density of CD68-positive macrophages in both tumor types, in pancreatic tumors they were concentrated mostly in the stroma and had much higher expression of VISTA.
The study findings suggest that combining a VISTA antibody to target macrophages might be a beneficial addition to pancreatic immunotherapy.