A Role for T-Lymphocytes in Human Breast Cancer and in Canine Mammary Tumors

Abstract

Chronic inflammation in the tumor microenvironment has a prominent role in carcinogenesis and benefits the proliferation and survival of malignant cells, promoting angiogenesis and metastasis. Mammary tumors are frequently infiltrated by a heterogeneous population of immune cells where T-lymphocytes have a great importance. Interestingly, similar inflammatory cell infiltrates, cytokine and chemokine expression in humans and canine mammary tumors were recently described. However, in both species, despite all the scientific evidences that appoint for a significant role of T-lymphocytes, a definitive conclusion concerning the effectiveness of T-cell dependent immune mechanisms has not been achieved yet. In the present review, we describe similarities between human breast cancer and canine mammary tumors regarding tumor T-lymphocyte infiltration, such as relationship of TILs and mammary tumors malignancy, association of ratio CD4+/ CD8+ T-cells with low survival rates, promotion of tumor progression by Th2 cells actions, and association of great amounts of Treg cells with poor prognostic factors. This apparent parallelism together with the fact that dogs develop spontaneous tumors in the context of a natural immune system highlight the dog as a possible useful biological model for studies in human breast cancer immunology.

CD4+, CD8+, FoxP3+ and HSP60+ Expressions in Cellular Infiltrate of Canine Mammary Carcinoma in Mixed Tumor

“…Our data are according to results that the carcinomas with high lymphocytic infiltrate exhibited shorter overall survival [2]. Besides, the high lymphocytic infiltrate can be associated with other poor prognostic factors, such as high histological grade, lymphatic invasion, and necrosis [16].…”

“…In the present study, it was observed that FoxP3+ labeling were distributed in the intratumoral region and in the inflammatory infiltrate. The increase of Treg in the tumor microenvironment may be related to factors of poor prognosis of mammary carcinomas, such as high histological grade, lymphatic invasion and necrosis, and lower survival rates for animals [2,16]. In addition, it has been suggested that Treg play a key role in the development of these tumors, since it would be linking immune suppression with tumor angiogenesis, together in the same biological program [1].…”

“…For this, 5 µm sections were mounted on silanized glass slides and subjected to antigen retrieval process (EnVision TMFlex Target Retrieval Solution High pH Code DM828) 2 or low pH (Code DM829) 2 for 20 min at 97ºC using the Dako pre-treatment (PT) link module 2 . The endogenous peroxidase activity was inhibited by peroxidase block 2 for 5 min, and slides received the anti-human CD4, anti-human CD8, anti--human FoxP3 and anti-human HSP60 murine monoclonal antibody 3 diluted 1:100 and incubated for 1h, at room temperature.…”

“…The endogenous peroxidase activity was inhibited by peroxidase block 2 for 5 min, and slides received the anti-human CD4, anti-human CD8, anti--human FoxP3 and anti-human HSP60 murine monoclonal antibody 3 diluted 1:100 and incubated for 1h, at room temperature. Then, slides were washed three times in phosphate buffered saline (PBS, pH 7.2), and then incubated with the reagent polymer (EnVision TMþ Dual LinkSystem/HRP) 2 for 30 min at room temperature and finally diaminobenzidine (DAB) 2 for 10 min. The sections were counterstained with Mayer's hematoxylin 2 and observed by optical microscopy atributting the scores absent (0), mild (1), moderate (2) or intense (3).…”

“…Then, slides were washed three times in phosphate buffered saline (PBS, pH 7.2), and then incubated with the reagent polymer (EnVision TMþ Dual LinkSystem/HRP) 2 for 30 min at room temperature and finally diaminobenzidine (DAB) 2 for 10 min. The sections were counterstained with Mayer's hematoxylin 2 and observed by optical microscopy atributting the scores absent (0), mild (1), moderate (2) or intense (3). In order to obtain the scores, all slides were analyzed by two observer and compared to control group.…”