Assistant Professor Small Animal Medical Oncology University of Pennsylvania School of Veterinary Medicine Philadelphia, Pennsylvania, United States
Abstract:
Background: Histiocytic sarcoma (HS) is a highly lethal malignancy. Increased tumor-infiltrating lymphocyte density has been positively associated with survival in canine HS patients, however, even patients with high numbers of intratumoral T cells ultimately succumb to their disease, suggesting the eventual failure of anti-tumor immunity.
Hypothesis/
Objectives: The objective of this study was to identify potential drivers of tumor progression and immunoevasion in canine HS.
Animals: Eighteen client-owned dogs diagnosed with localized HS of variable anatomic locations.
Methods: Archived HS tumors were retrospectively identified. RNA extraction was performed on a subset of tumors from patients with short and long survival times and isolated RNA was subjected to NanoString immune transcriptional profiling and compared to RNA isolated from healthy control tissues. All 18 samples were subsequently stained for osteopontin using immunohistochemistry to assess expression at a protein level and digital images were captured.
Results: Immune transcriptional profiling of HS tumors revealed SPP1 (osteopontin) to be the most upregulated gene expressed in canine HS samples. Osteopontin protein was expressed variably in all canine HS tumors with the strongest expression noted in peri-articular tumors.
Conclusions and clinical importance: We demonstrated overexpression of osteopontin at a transcriptional and protein level implicating a potential pro-tumorigenic role for this protein in canine HS. Previous literature reports a T cell suppressive role of osteopontin, and future studies are planned to determine the functional effect of osteopontin exposure on canine T cells.
