Potential Tool for Prognosticating in Canine Mammary Gland Tumors
Cheryl Balkman, DVM, MS, DACVIM (Internal Medicine, Oncology), Cornell University
In the Literature
Ariyarathna H, Thomson NA, Aberdein D, Perrott MR, Munday JS. Increased programmed death ligand (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) expression is associated with metastasis and poor prognosis in malignant canine mammary gland tumors. Vet Immunol Immunopathol. 2020;230:110142.
The Research …
Immunosurveillance helps identify infected or abnormal cells. Signaling molecules, collectively referred to as immune checkpoint molecules, on T lymphocytes help regulate immunosurveillance and can be either activating or inhibitory. Inhibitory immune checkpoint molecules, which suppress T lymphocyte activation, are aberrantly expressed in many human cancers. Suppression may allow tumors to evade the host immune surveillance, allowing more aggressive clinical behavior.
Two inhibitory immune checkpoint molecules often expressed in human tumors are programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4)1,2; these molecules are associated with more aggressive behavior and worse prognosis, and measuring their expression on tumors may help provide a more accurate prognosis.3,4 A variety of canine tumors express PD-L1 and CTLA-4, which have been shown to be prognostic in canine high-grade B-cell lymphoma.5 PDL-1 is detected more frequently in malignant than benign mammary gland tumors,6,7 but association with prognosis has not been reported.
This study investigated the immunostaining and gene expression of PDL-1 and CTLA-4 in 41 histologically malignant and 12 benign canine mammary gland tumors with known outcomes. The goal was to determine whether PDL-1 and CTLA-4 immunostaining and gene expression are correlated with biologic behavior and clinical outcome. Metastasized malignant mammary gland tumors had significantly higher immunostaining scores and gene expression for both PDL-1 and CTLA-4 than nonmetastasized malignant tumors.
On multivariate analysis, PDL-1 and tumor grade were independent prognostic indicators of survival; CTLA-4, tumor size, and tumor emboli were not independent prognostic indicators of survival.
… The Takeaways
Key pearls to put into practice:
Canine malignant mammary gland tumors are a heterogeneous group of tumors with biological behavior that can be difficult to predict.
Different prognostic factors, including histologic subtype, tumor grade, and stage, have been evaluated, but additional factors likely play a role in the aggressive behavior of a tumor.
Results of this study show PDL-1 and CTLA-4 immunostaining of mammary gland tumors may allow better prognostication in dogs and could lead to development of future therapeutics.