VISTA checkpoint implicated in pancreatic cancer immunotherapy resistance

ScienceDaily | 1/11/2019 | Staff
Tanya9 (Posted by) Level 3
The University of Texas MD Anderson Cancer Center research team found overexpression of the immune checkpoint VISTA on immune cells, especially macrophages, that infiltrated pancreatic tumors. Their paper will be published online Friday at the Proceedings of the National Academy of Sciences.

"VISTA is a potential therapeutic target in pancreatic cancer, and there are several antibodies to block VISTA under clinical development," said co-senior author Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology. "Additional research also needs to be done to see if we can come up with other targets for these VISTA-positive cells as well."

Checkpoint - Inhibitors - Attack - Cancer - PD-1

Present immune checkpoint inhibitors that unleash an immune attack on cancer by blocking PD-1 and CTLA-4 brakes on T cells have been ineffective against pancreatic cancer, one of the most lethal cancers. The five-year survival rate for patients with pancreatic cancer is 7 percent or less.

The team, led by Sharma and 2018 Nobel Laureate Jim Allison, Ph.D., professor and chair of Immunology, set out to shed light on infiltration of immune cells and expression of immunity-inhibiting checkpoints in pancreatic cancer by comparing those tumors to melanoma, the cancer that is most vulnerable to immune checkpoint blockade.

Expression - Inhibitory - Genes - Cancer - Tumors

They first analyzed expression of nine immune inhibitory genes in 23 untreated, surgically removed pancreatic cancer tumors and found the results separated the patients into two groups, 11 with high-expression of inhibitory genes and 12 with low expression.

Those with low-expression of immune inhibitors had a median survival of 37 months versus 20 months for the high-expression group, indicating potential immune impact on overall survival.

Cancer - Tumors - Density - Stroma - Cells

Pancreatic cancer tumors include a high density of stroma, non-malignant supportive cells, while melanoma is at the other end of the spectrum with minimal stroma. These differences came into play in the team's analyses. The pancreatic tumors were composed of 30 percent malignant cells and...
(Excerpt) Read more at: ScienceDaily
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