V-domain immunoglobulin suppressor of T-cell activation (VISTA) is constitutively expressed in hematopoietic lineage and is highly up-regulated in tumor infiltrated myeloid cells and regulatory T-cells in animal models. However, its expression in human pancreatic tumor microenvironment remains unknown. In this research, we aimed at the expression of VISTA in human pancreatic cancer samples. METHODS: We performed immunohistochemistry to determine VISTA expression in human pancreatic cancer samples. RESULTS: We found that 88.46% of the patients showed high-density infiltration of polymorphonuclear neutrophils and mononuclear immune cells with up-regulated expression of VISTA in cancer tissues, especially in the necrotic foci. Interestingly, it was minimally expressed in pancreatic cancerous cells and was not detectable in either normal ducts or islet cells in cancerous or normal pancreatic tissues. CONCLUSIONS: We conclude that VISTA is predominantly expressed and up-regulated in the high-density infiltrated immune cells but minimal in human pancreatic cancerous cells. Our results for the first time highlight pancreatic immunosuppressive tumor microenvironment contributed by VISTA and its potential as a prominent target for pancreatic cancer immunotherapy.
V-domain immunoglobulin suppressor of T-cell activation (VISTA) is constitutively expressed in hematopoietic lineage and is highly up-regulated in tumor infiltrated myeloid cells and regulatory T-cells in animal models. However, its expression in humanpancreatic tumor microenvironment remains unknown. In this research, we aimed at the expression of VISTA in humanpancreatic cancer samples. METHODS: We performed immunohistochemistry to determine VISTA expression in humanpancreatic cancer samples. RESULTS: We found that 88.46% of the patients showed high-density infiltration of polymorphonuclear neutrophils and mononuclear immune cells with up-regulated expression of VISTA in cancer tissues, especially in the necrotic foci. Interestingly, it was minimally expressed in pancreatic cancerous cells and was not detectable in either normal ducts or islet cells in cancerous or normal pancreatic tissues. CONCLUSIONS: We conclude that VISTA is predominantly expressed and up-regulated in the high-density infiltrated immune cells but minimal in humanpancreatic cancerous cells. Our results for the first time highlight pancreatic immunosuppressive tumor microenvironment contributed by VISTA and its potential as a prominent target for pancreatic cancer immunotherapy.
Authors: Nishant Mehta; Sainiteesh Maddineni; Ryan L Kelly; Robert B Lee; Sean A Hunter; John L Silberstein; R Andres Parra Sperberg; Caitlyn L Miller; Amanda Rabe; Louai Labanieh; Jennifer R Cochran Journal: Sci Rep Date: 2020-09-16 Impact factor: 4.379