Immunohistochemical profiling of VISTA expression in canine mammary tumors: A pilot study for immunotherapeutic targeting.

Abstract

VISTA (V-domain Ig-containing suppressor of T cell activation) is an immune checkpoint protein that regulates the activity of T cells and is involved in immune tolerance. Although its role has been elucidated in human oncology, its significance in canine mammary tumors (CMTs) is unclear. This research was focused on investigating VISTA expression in CMTs and its correlation with histologic grade and molecular subtype. Archived formalin-fixed, paraffin-embedded mammary gland tumors taken from 26 canine patients diagnosed with malignant tumors were studied. Histopathologic classification and grading were performed using hematoxylin and eosin-stained sections. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), HER2, and VISTA was done, and molecular subtypes were defined as based on ER, PR, and HER2 status. VISTA immunoreactivity was semiquantitatively evaluated in tumor cells and in inflammatory cells. VISTA expression in neoplastic cells and in cells of the inflammatory infiltrate was found. Increased tumor grade was found to have significantly increased VISTA staining intensity and overall score in tumor cells. Inflammatory cell staining differed according to grade, yet this difference was not significant. No significant difference in VISTA expression was detected in molecular subtypes. This is the initial research to shed light on VISTA expression in CMTs. Its identification within tumor cells and within cells of the infiltrate, and its correlation with tumor grade, places its importance as an immunotherapeutic and prognostic marker in mammary cancer in dogs.