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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. Our results revealed several notable factors, including the significantly higher levels of CD3+ T cells and CD8+ T cells within tumour cell nests in cases treated with preoperative COX inhibitors compared to untreated cases. Based on the immunohistochemistry data, we further performed a comparative analysis using publicly available RNA‐seq data from untreated cUC tissues (n = 29) and normal bladder tissues (n = 4) to explore the link between COX–prostanoid pathways and the immune response to tumours. We observed increased expression of COX‐2, microsomal prostaglandin E2 synthase‐1 (mPGES‐1) and mPGES‐2 in cUC tissues. However, only mPGES‐2 showed a negative correlation with the cytotoxic T‐cell (CTL)–related genes CD8A and granzyme B (GZMB). In addition, a broader analysis of solid tumours using The Cancer Genome Atlas (TCGA) database revealed similar patterns in several human tumours, suggesting a common mechanism in dogs and humans. Our results suggest that the COX‐2/mPGES‐2 pathway may act as a cross‐species tumour‐intrinsic factor that weakens anti‐tumour immunity, and that COX inhibitors may convert TIME from a 'cold tumour' to a 'hot tumour' state by counteracting COX/mPGES‐2–mediated immunosuppression. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is a rare neoplasm of macrophages or dendritic cells with a poor prognosis in dogs. As the apoptosis inhibitor of macrophage (AIM) is characteristically expressed in canine macrophages, we hypothesised that AIM is involved in the development or progression of HS in dogs. In this study, AIM expression in the tumour region and serum AIM levels in dogs with HS was assessed. Additionally, the effects of AIM overexpression on HS cell viability were investigated using a HS cell line that was selected from five validated HS cell lines. Immunohistochemistry showed that AIM expression was observed in the cytoplasm of the HS cells. CD36, a candidate AIM receptor, was also observed on the cell membrane of HS cells. When the serum AIM level was detected in 36 dogs with HS and 10 healthy dogs via western blot analysis, the AIM levels in the HS dogs were significantly higher than those in the controls. AIM mRNA expression in the 5 HS cell lines varied but was higher than that in the other tumour‐derived lines. Among the five HS cell lines, DH82 originally had lower AIM and the highest CD36 expression. When AIM was overexpressed in DH82, therein cell growth speed and invasion, apoptosis inhibition and phagocytic activity were strongly upregulated. These data suggest that elevated intra‐tumour expression of AIM could induce the progression of HS cells in dogs. Moreover, elevated serum AIM levels in dogs with HS could serve as a biomarker of HS. [ABSTRACT FROM AUTHOR]

The cover image is based on the article Comprehensive Analysis of the Tumour Immune Microenvironment in Canine Urothelial Carcinoma Reveals Immunosuppressive Mechanisms Induced by the COX‐Prostanoid Cascade by Shotaro Eto et al., https://doi.org/10.1111/vco.12999. [ABSTRACT FROM AUTHOR]