Comprehensive Analysis of the Tumour Immune Microenvironment in Canine Urothelial Carcinoma Reveals Immunosuppressive Mechanisms Induced by the COX-Prostanoid Cascade.

A comprehensive understanding of the tumour immune microenvironment (TIME) is essential for advancing precision medicine and identifying potential therapeutic targets. This study focused on canine urothelial carcinoma (cUC) recognised for its high sensitivity to cyclooxygenase (COX) inhibitors. Using immunohistochemical techniques, we quantified the infiltration of seven immune cell populations within cUC tumour tissue to identify clinicopathological features that characterise the TIME in cUC.

Pan-tumour analysis of COX-2 expression in dogs.

Cyclooxgenase-2 (COX-2) is associated with inflammatory microenvironment and tumour progression. COX-2 expression was reported in canine tumours, and anti-COX treatment showed therapeutic effects in selected tumour types. Currently, direct comparisons between different tumour types or reports were impossible due to varying evaluation protocols.

Tumor cell-derived spermidine is an oncometabolite that suppresses TCR clustering for intratumoral CD8 T cell activation.

The activation and expansion of T cells that recognize cancer cells is an essential aspect to antitumor immunity. Tumors may escape destruction by the immune system through ectopic expression of inhibitory immune ligands typically exemplified by the PD-L1/PD-1 pathway. Here, we reveal another facet of tumor evasion from T cell surveillance.

Potential of HMGB-inhibitory oligodeoxynucleotide ISM ODN to neutrophil recruitment in mouse model of hepatitis.

High-mobility group box 1 (HMGB1) is a nucleotide-binding chromatin protein that has also been characterized as a prototypical damage-associate molecular pattern. It triggers inflammatory responses upon release from damaged or dying cells. In fact, HMGB1 has been linked to the induction of many inflammatory diseases through immune cell activation including neutrophil recruitment.

Anti-CCR4 treatment depletes regulatory T cells and leads to clinical activity in a canine model of advanced prostate cancer.

Background: Targeting regulatory T cell (Treg) infiltration is an emerging strategy for cancer immunotherapy. However, its efficacy in advanced prostate cancer remains unclear. Here, we showed the therapeutic efficacy of anti-Treg treatment in a canine model of advanced prostate cancer.

Detection of indoleamine 2,3-dioxygenase 1-expressing cells in canine normal and tumor tissues.

Cancer immunotherapy is a novel cancer treatment for canine tumors. Indoleamine 2,3-dioxygenase 1 (IDO1) is overexpressed in some human tumors and inhibits antitumor immunity. In this study, we comprehensively evaluated expression pattern of IDO1 and the nature of IDO1-expressing cells in canine normal and tumor tissues.

Expression of podoplanin in various types of feline tumor tissues.

Podoplanin is expressed in various human tumors where it promotes tumor progression, epithelial-mesenchymal transition, and distant metastasis. Podoplanin is also expressed in cancer-associated fibroblasts and induces tumor malignancy. The objective of this study was to evaluate podoplanin expression in various types of feline tumor tissues.

The impact of damage-associated molecules released from canine tumor cells on gene expression in macrophages.

Dying or damaged cells that are not completely eradicated by the immune system release their intracellular components in the extracellular space. Aberrant exposure of the damage-associated molecules to the immune system is often associated with inflammation and cancer pathogenesis. Thus, elucidating the role of damage-associated molecules in inducing sterile immune responses is crucial.

Phase I/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma.

Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed on tumor cells. PDPN is known to be linked with several aspects of tumor malignancies in certain types of human and canine tumors. Therefore, it is considered to be a novel therapeutic target.

BRAF Mutation Associates CCL17 Expression and Regulatory T Cell Recruitment in Urothelial Carcinoma of Dogs.

Regulatory T cells may serve as targets in cancer immunotherapy. A previous study showed that the chemokine CCL17 and the receptor CCR4 play roles in regulatory T cell recruitment in canine urothelial carcinoma. In this article, we show that the BRAF mutation is associated with tumor-produced CCL17 and regulatory T cell infiltration in dogs with urothelial carcinoma.

Author Correction: Aberrant expression of the COX2/PGE axis is induced by activation of the RAF/MEK/ERK pathway in BRAF canine urothelial carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Aberrant expression of the COX2/PGE axis is induced by activation of the RAF/MEK/ERK pathway in BRAF canine urothelial carcinoma.

Cancer-promoting inflammation is an important event in cancer development. Canine urothelial carcinoma (cUC) overexpresses prostaglandin E (PGE) and has a unique sensitivity to cyclooxygenase 2 (COX2)-inhibiting therapy. In addition, majority of cUC harbour BRAF mutation.

PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma.

Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed. It is also known to be linked with several aspects of tumor malignancy in some types of human tumors, including invasion, metastasis, and cancer stemness. However, there are few reports on the expression of dog PDPN (dPDPN) in canine tumors, and the association between dPDPN and tumor malignancy has not been elucidated.

Overexpression of human epidermal growth factor receptor 2 in canine primary lung cancer.

Human epidermal growth factor receptor 2 (HER2) overexpression has been reported in various human cancers. HER2-targeted therapies showed clinical responses in humans with HER2-positive tumors. The incidence of canine primary lung cancer (cPLC) is increasing, but there are no effective systemic therapies for dogs with late-stage cPLC.

Immunohistochemical evaluation of HER2 expression in canine thyroid carcinoma.

The human epidermal growth factor receptor 2 (HER2) is expressed in various human cancers including thyroid cancers (TC) and is used as a diagnostic marker and therapeutic target. Canine TC (cTC), the most common endocrine malignancy in dogs, shows a high metastasis rate, and HER2-targeted therapy could be a candidate for treatment. Here, we immunohistochemically evaluated HER2 expression in 21 paraffin-embedded cTC tissues and scored the degree of expression based on intensity and positivity (score: 0-3+).

Anti-tumor effects of the histone deacetylase inhibitor vorinostat on canine urothelial carcinoma cells.

Canine urothelial carcinoma (cUC) is the most common tumor of the lower urinary tract in dogs. Although chemotherapy and radical surgery have improved the overall survival, most dogs with cUC succumb to metastasis or recurrence. Therefore, the development of an effective systematic therapy is warranted.

Detection of human epidermal growth factor receptor 2 overexpression in canine anal sac gland carcinoma.

Canine anal sac gland carcinoma (ASGC) frequently occurs in the apocrine glands of the canine anal sac and shows aggressive biological behavior. The expression of human epidermal growth factor receptor 2 (HER2) has been reported in various human and canine tumors. HER2 is a promising therapeutic target of these tumors, and HER2-targeted drugs, such as trastuzumab and lapatinib, have improved the outcome of these patients.

Aldehyde dehydrogenase activity helps identify a subpopulation of murine adipose-derived stem cells with enhanced adipogenic and osteogenic differentiation potential.

Aim: To identify and characterize functionally distinct subpopulation of adipose-derived stem cells (ADSCs).

Methods: ADSCs cultured from mouse subcutaneous adipose tissue were sorted fluorescence-activated cell sorter based on aldehyde dehydrogenase (ALDH) activity, a widely used stem cell marker. Differentiation potentials were analyzed by utilizing immunocytofluorescece and its quantitative analysis.

Aldehyde dehydrogenase activity identifies a subpopulation of canine adipose-derived stem cells with higher differentiation potential.

Adipose-derived stem cells (ADSCs) are abundant and readily obtained, and have been studied for their clinical applicability in regenerative medicine. Some surface antigens have been identified as markers of different ADSC subpopulations in mice and humans. However, it is unclear whether functionally distinct subpopulations exist in dogs.

Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 in a dog.

Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 were diagnosed in a 6-month-old female Pomeranian with tetraplegia as a clinical sign. Lateral survey radiography of the neck with flexion revealed atlantoaxial subluxation with ventral subluxation of C2. Computed tomography revealed absence of dens and atlanto-occipital overlapping.