Decreased Ratio of CD8+ T Cells to Regulatory T Cells Associated with Decreased Survival in Dogs with Osteosarcoma

Abstract

Background Increased numbers of regulatory T cells (Treg) and decreased ratios of CD8+ T cells to Treg have been shown to correlate with decreased survival times (ST) in humans with certain malignancies. A possible connection between Treg and ST in dogs with cancer has not been investigated previously. Hypothesis The purpose of this study was to compare numbers of Treg and T lymphocyte subsets in dogs with osteosarcoma (OSA) to those of healthy dogs and to determine whether pretreatment values were associated with disease-free interval or with ST. We hypothesized that Treg numbers would be increased in dogs with cancer and that dogs with a high percentage of Treg would have a poorer prognosis. Animals Twelve client-owned dogs with appendicular OSA were entered into a prospective clinical trial. Twenty-two healthy dogs were used as controls. Methods The percentages and numbers of Treg and CD4+ and CD8+ T cells in blood, lymph nodes, and tumors were determined with flow cytometry and compared between dogs with OSA and control dogs. Results Dogs with OSA had significantly fewer circulating CD8+ T cells and significantly more Treg compared with healthy dogs. The CD8/Treg ratio also was significantly lower in dogs with OSA compared with control dogs. In dogs with OSA, a decreased CD8/Treg ratio was associated with significantly shorter STs. Conclusions These data support a role for Treg in the immune control of canine OSA and suggest that determination of the CD8/Treg ratio may be useful for assessing outcomes.

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

“…Interestingly, CD8 + /FOXP3 + -ratio in biopsies prior chemotherapy allows the identification of patients with prolonged survival confirming the results previously obtained in dogs [79,80]. The data revealed that patients with a CD8 + /FOXP3 + -ratio above 3.08 had an improved survival what strengthened the key function played by T-lymphocyte infiltrates in the pathogenesis of osteosarcoma [80].…”

“…The data revealed that patients with a CD8 + /FOXP3 + -ratio above 3.08 had an improved survival what strengthened the key function played by T-lymphocyte infiltrates in the pathogenesis of osteosarcoma [80]. The identification of tumor-specific lymphocytes has led to the development of immunotherapeutic approaches based on the recovery of an effective and sustained anti-tumor immune response in patients [81,82].…”

Osteosarcoma in Dogs: Diagnosis and Treatment - A Literature Review

“…Biller et al [27] show that T-cell effector (CD4 + and CD8 +) and regulatory (Treg) cells are responsible for both T lymphocytes and tumors. This study, the percentage and number of Treg, CD4+ and CD8+ cells were measured in blood by flow cytometry in lymph nodes and tumors by flow cytometry and compared between dogs with OSA and clinically healthy.…”

“…This professional informs the patient about his health condition in a clear way and makes him more involved in the treatment, being able to manage his own health, with changes of life habits in order to improve his prognosis [25][26][27][28][29]. In veterinary medicine, this professional is still not very present, especially in developing countries, and changes in patient's life habits depend on the actions of their owner, since he is responsible for their eating and physical activities outside the home environment.…”

“…Finally, 290 articles were selected, and with the reading of the abstracts, 63 articles were selected to read the full text, of these [27], were used, as they followed the objective of this study. The incidence of OSA in dogs, the techniques used in the diagnosis and treatment of in vivo and in vitro studies are described in chronological order in Table 1.…”