The Expression of Selected Factors Related to T Lymphocyte Activity in Canine Mammary Tumors

Abstract

Crosstalk between neoplastic and immune cells in the tumor microenvironment (TME) influences the progression of disease in human and canine cancer patients. Given that canine mammary tumors are a useful model to study breast cancer biology, we aimed to evaluate the expression of genes associated with T lymphocyte activity in benign, malignant, and metastatic canine mammary tumors. Interestingly, metastatic tumors exhibit increased expression of CXCR3, CCR2, IL-4, IL-12p40, and IL-17. In particular, we focused on IL-17, a key interleukin associated with the Th17 lymphocyte phenotype. Th17 cells have been shown to play a contradictory role in tumor immunity. Although IL-17 showed a high expression in the metastatic tumors, the expression of RORγt, a crucial transcription factor for Th17 differentiation was barely detected. We further investigated IL-17 expression using immunohistochemistry, through which we confirmed the increased expression of this interleukin in malignant and metastatic mammary tumors. Finally, we compared the plasma levels of IL-17 in healthy and malignant mammary tumor-bearing dogs using ELISA but found no differences between the groups. Our data indicate that the IL-17 in metastatic tumors may be produced by other cell types, but not by Th17 lymphocytes. Overall, our results broaden the available knowledge on the interactions in canine mammary tumors and provide insight into the development of new therapeutic strategies, with potential benefits for human immune oncology.

Comparison of mucin-1 in human breast cancer and canine mammary gland tumor: a review study

“…In molecular level, the expression of programmed death-ligand 1 (PDL1) and PDL2 two co-inhibitory molecule- have been examine in CMT cells. PDL2 expression is reduced in CMT metastatic tumors, similar phenomenon happens for PDL1 expression in metastatic HBC [ 10 ]. Gal9 boosts anti-tumor immunity mediated Th1 cells in HBC and CMT [ 10 ].…”

“…PDL2 expression is reduced in CMT metastatic tumors, similar phenomenon happens for PDL1 expression in metastatic HBC [ 10 ]. Gal9 boosts anti-tumor immunity mediated Th1 cells in HBC and CMT [ 10 ]. Gal9 is a prognostic marker in both models and in human, gal9 expression is negatively related to distant metastasis, moreover, in CMT, gal9 expression in reduced in tumor cells [ 10 ].…”

“…According to several research results, not only the composition of immune cells in tumor microenvironment in HBC and CMT is alike, but also results demonstrate a parallel expression pattern of immune molecules in both tumors [ 10 ]. In cellular level, CMT cells like HBC cells show high number of neutrophil cells [ 55 ], TAMs [ 10 , 56 ], and CD4 + [ 12 , 55 , 56 ] cells which are associated with metastasis [ 55 , 56 ]. Furthermore, high number of plasma cells, macrophages, CD8+ are negatively related to metastasis [ 55 ].…”

“…Many scientists believe that CMT is a perfect model for HBC investigations [ 9 , 10 ]. CMT can be used for the evaluation of immunotherapy and other therapeutic applications [ 10 ]. Accordingly, this review drew a comparison between the MUC-1 roles in HBC and CMTs as a model for human studies.…”

Association Between Tumor Mutation Burden and Prognosis in Lower-Grade Glioma: An Exploratory Study 

“…Furthermore, Gorsi reported that immune checkpoint inhibitors (Nivolumab) performed better in brain tumor patients with higher TMB [6] . Besides, crosstalk between neoplastic and immune cells in the TME also in uences the progression of disease in humans [7] . Accumulating evidence shows that TMB and TME can be exploited to predict the clinical outcomes and therapeutic responses of the tumor.…”