Changes in Regulatory T Cells in Dogs with Cancer and Associations with Tumor Type

Abstract

Background: Regulatory T cells (Treg) have been shown to suppress antitumor immunity and often are increased in humans and rodents with cancer. However, Tregs have not been well studied in dogs with cancer and it is not known if certain tumor types are associated with increased Tregs.Hypothesis: We hypothesized that Treg percentages would be increased in dogs with cancer and that Treg percentages would be higher in dogs with certain types of cancer.Animals: The percentages and numbers of Tregs and nonregulatory T cells and B cells were assessed in 34 dogs with cancer and 9 age-matched control dogs. Dogs evaluated included 14 dogs with sarcoma, 7 dogs with carcinoma, 7 dogs with lymphoma, and 6 dogs with mast cell tumor.Methods: Numbers and percentages of Tregs, CD4 1 , and CD8 1 T cells and B cells were determined using flow cytometry and compared between control dogs and dogs with cancer.Results: The percentage of Tregs was significantly increased overall in dogs with cancer compared with control dogs. When tumor types were compared, Treg percentages were significantly increased in dogs with carcinoma. The Treg/CD8 T cell ratio was significantly higher in dogs with cancer compared with control dogs and was also significantly increased in 2 dogs with T-cell lymphoma.Conclusions: Treg percentages in blood were increased in dogs with cancer, particularly in dogs with carcinoma. The Treg/ CD8 ratio also identified tumor-specific abnormalities in dogs with cancer. These findings indicate that tumor-specific factors may affect Tregs in dogs.

Regulatory T cells in dogs with multicentric lymphoma: peripheral blood quantification at diagnosis and after initial stage chemotherapy

“…Similar results have been previously reported by O'Neill et al (2009), who analysed dogs with various types of neoplasia (sarcoma, carcinoma, lymphoma and mastocytoma) and by Mitchell et al (2012) in dogs with type B lymphoma. On the other hand, other studies (Winnicka et al, 2002;Walter et al, 2006) have reported significant differences between healthy and neoplastic dogs and have attributed such differences to factors related to the tumours, suggesting that these tumours can be suppressive; however, no information on the type of suppression was provided (Winnicka et al, 2002).…”

“…Firstly, the way of expressing the results could be one of these factors since the relative values of CD4 + and CD8 + were transformed into absolute values (in relation to the number of lymphocytes obtained in the haemogram) (Winnicka et al, 2002). Another factor would be to analyse together data from different types of tumours, as described by O'Neill et al (2009). Lastly, patients with one type of tumour with various histological classifications and immunophenotypes, such as lymphoma, could be analysed the same way by the same analysis.…”

Quantification of Treg cells in peripheral blood and lymph nodes of dogs with multicentric lymphoma

“…In veterinary medicine, some authors observed a significant increase in Tregs of dogs with cancer compared to healthy dogs (O'Neill et al, 2009). Other authors found that Tregs were significantly higher in dogs with metastatic tumors than in dogs with nonmetastatic tumors (Horiuchi et al, 2009).…”

“…In dogs, a number of research articles have been published based upon changes in CD4 + and Foxp3 + proportion of cells that occur in tumors (Gereda et al, 2000;Biller et al, 2007;O'neill et al, 2009;Horiuchi et al, 2009;Rissetto et al, 2010;Biller et al, 2010;Tominaga et al, 2010). A study comparing the percentage of Tregs between healthy dogs and those with diverse tumors such as round cell tumors, sarcomas and carcinomas, showed a higher Tregs expression both in peripheral blood and tumor tissue (Biller et al, 2007).…”

“…Natural Regulatory T cells express CD4 and CD25 (high affinity to interleukin-2 receptors) and are also transcribed by the Foxp3 factor (Banham et al, 2009). In dogs, Tregs were identified using specific antibodies against canine CD4 and murine Foxp3 (Biller et al, 2007;Keppel et al, 2008;Banham et al, 2009;Horiuchi et al, 2009;O'neill et al, 2009). …”