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VISTA Checkpoint Implicated in Pancreatic Cancer Immunotherapy Resistance

Researchers have identified a new potential immunotherapy target in pancreatic cancer, which so far has been notoriously resistant to treatment with immune checkpoint blockade drugs effective against a variety of other cancers. A research team from The University of Texas MD Anderson Cancer Center found overexpression of the immune checkpoint VISTA on immune cells, especially macrophages, that infiltrated pancreatic tumors. Their findings were published by Blando et al in Proceedings of the National Academy of Sciences.1

VISTA is a potential therapeutic target in pancreatic cancer, and there are several antibodies to block VISTA under clinical development.

— Padmanee Sharma, MD, PhD

“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, MD, PhD, Professor of Genitourinary Medical Oncology and Immunology at MD Anderson. “Additional research also needs to be done to see if we can come up with other targets for these VISTA-positive cells as well.”

Present immune checkpoint inhibitors that unleash an immune attack on cancer by blocking programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) brakes on T cells have been ineffective against pancreatic cancer.

The team, led by Dr. Sharma and James Allison, PhD, Professor and Chair of Immunology at MD Anderson, set out to shed light on the 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.

They first analyzed expression of 9 immune inhibitory genes in 23 untreated, surgically removed pancreatic cancer tumors and found the results separated the patients into 2 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 vs 20 months for the high-expression group, indicating a potential immune impact on overall survival.

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