Page 1270 - Clinical Small Animal Internal Medicine

1208 Section 11 Oncologic Disease

treatments that can result in transient or chronic effects. The function of effector T cells and APCs can be dis-
VetBooks.ir Clinical examples of local and systemic inflammatory rupted by a T lymphocyte type, known as regulatory T
cell (Treg). Treg cells are important for immune toler-
reactions to oncologic treatments in veterinary medicine
would include localized oral mucositis within the radia-
cytes; however, suppression of antitumor immune
tion field and generalized intestinal inflammation with ance through downregulation of self‐reactive lympho-
certain chemotherapeutic agents, respectively. responses by Tregs can promote tumor progression and
The association between chronic inflammation and development. Large populations of Tregs have been
neoplasia is well established. Some recent interesting shown to be present in various human cancers and to
examples of chronic inflammatory lesions that progress correlate with poor prognosis. The involvement of
to cancer in veterinary medicine include biliary tract Tregs in veterinary oncology has been investigated in a
trematode infection leading to cholangiocarcinoma in number of different canine tumor types. In these stud-
cats, superficial corneal squamous cell carcinoma occur- ies, the numbers of Treg cells in the peripheral blood
ring in dogs with chronic keratitis, and traumatic or and tumor‐draining lymph nodes were increased in
surgical fracture‐associated osteosarcoma development dogs with cancer compared to healthy dogs. Further,
in dogs. Treg cell infiltration was statistically correlated with
A nonspecific and complex host response to inflam- high histologic grade in canine mammary carcinoma.
mation that has been investigated for its potential use as Many therapeutic approaches have been developed
a prognostic and monitoring tool is the formation of that utilize the immune system to target and treat cancer,
acute phase proteins (APP). APPs are induced by proin- and these techniques have been explored in veterinary
flammatory cytokines, and tumor cells produce large oncology. Nonspecific tumor immunotherapies, includ-
amounts of transforming growth factor beta, cytokines ing biologic response modifiers, such as bacterial strains,
including interleukins 6 and 10, and prostaglandin E2. oncolytic viruses, and recombinant cytokines, growth
Veterinary studies evaluating the use of APPs include tri- factors, and hormones, have been used to treat several
als with canine and feline lymphoma, canine mammary veterinary malignancies. Also, specific targeted immu-
carcinoma, mast cell tumors, soft tissue sarcoma, and notherapies, such as cancer vaccines, where the immune
combinations of tumor‐bearing dogs and cats. system detects tumors through tumor‐associated anti-
A targeted approach to inhibiting the inflammatory gens, have been utilized for veterinary patients. Clinical
component of cancer that is commonly used in veteri- examples of veterinary cancer vaccines include the
nary oncology is the use of cyclooxygenase (COX) xenogeneic DNA vaccine for canine melanoma and the
inhibitors, specifically those that inhibit the enzyme autologous tumor RNA‐loaded, activated B cell vaccine
COX‐2. Overexpression of COX‐2 in tumors drives for canine lymphoma.
many cancer‐associated mechanisms and COX‐2 inhib-
itors are prescribed to prevent or reduce the neoplastic
proinflammatory state. The effects of the COX‐inhibi- Inducing Angiogenesis
tor piroxicam have been evaluated in the treatment of
canine urinary bladder transitional cell carcinoma, as Tumor vasculature is unique and abnormal. In order for
well as canine oral malignant melanoma, inflammatory a developing solid tumor to grow into a macroscopic
mammary carcinoma, prostatic carcinoma, and oral mass, it must induce the surrounding normal tissue to
squamous cell carcinoma. either share its oxygen and nutrient supply or create its
own vascular network. The processes by which a tumor
forms new blood vessels, known as vasculogenesis, and/
Avoiding Immune Destruction or remodels existing vasculature, known as angiogenesis,
involve highly integrated signaling and communication
Cancer develops in the host through deception of the between cells of the microenvironment. Tumors stimu-
immune system. The roles of the immune cells are late persistent angiogenesis through expression of many
defined by their involvement in either innate or adaptive factors, one of the most important being the family of
immunity. Cells of the innate pathway include phago- vascular endothelial growth factor (VEGF) proteins.
cytic, antigen‐presenting cells (APC), such as mac- Vascular endothelial growth factor is a growth factor
rophages and dendritic cells, and those of the adaptive and its signal is transmitted through the tyrosine kinase
pathway consisting of cells with randomly generated activity of transmembrane VEGF receptors. Most cancer
antigen receptors, like B and T lymphocytes. Generally, cells and certain tumor stromal cells express VEGF, and
APCs are activated by immunogenic stimuli, migrate to stimulation of VEGF leads to endothelial cell prolifera-
lymphoid organs to present antigen to T cells, and stimu- tion, migration, and survival. In veterinary oncology,
late the adaptive immune response. VEGF expression has been recognized as a negative