# Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value—A Review

## TL;DR

This review explores the tumor microenvironment in feline mammary tumors, highlighting its role in cancer progression and potential for improving diagnosis and treatment.

## Contribution

The paper provides a comprehensive review of the feline mammary tumor microenvironment, linking it to human breast cancer insights for better prognosis and therapy.

## Key findings

- Feline mammary tumors show associations between collagen remodeling and poor prognosis.
- Regulatory T cells and elevated leptin correlate with worse outcomes in feline mammary carcinoma.
- Stromal cytotoxic T cells are linked to more favorable prognostic outcomes.

## Abstract

The tumor microenvironment has become a central focus in cancer research, offering new insights into cancer behavior and showing strong potential for improving cancer treatment. However, in veterinary oncology, specifically feline mammary tumors, research on the topic lags far behind. This review summarizes current knowledge on key elements of the tumor microenvironment in the feline mammary tumors, including tumor necrosis, fibrosis, angiogenesis, adipose tissue, tumor-associated inflammation, extracellular vesicles, and epithelial–mesenchymal transition. Although studies in cats remain limited, insights from human breast cancer are frequently drawn, creating a combined perspective that may help drive new research into the diagnostic, prognostic, and therapeutic potential of the tumor microenvironment in feline mammary tumors.

The tumor microenvironment (TME) comprises neoplastic and stromal cells, and extracellular matrix elements, all engaging in a complex interplay that ultimately dictates tumorigenesis, cancer progression, and therapeutic response. While extensive research on the TME has been conducted in human oncology, data on its veterinary counterpart, particularly in feline mammary tumors (FMTs), are still scarce. In this review, we explore current understanding of feline mammary carcinoma (FMC) microenvironment, focusing on tumor necrosis, fibrosis, angiogenesis, adipose tissue tumor-associated inflammation, extracellular vesicles, and epithelial–mesenchymal transition (EMT) and their prognostic implications. In FMC, remodeling of collagen fibers, cancer-associated fibroblasts (CAFs), regulatory T cells (Tregs) and elevated serum leptin have been associated with poor prognosis, whereas stromal cytotoxic T cells correlate with more favorable outcomes. By contrast, findings on necrosis and pro-angiogenic factors remain inconsistent, and research on extracellular vesicles (EVs) is still in its early stages. This review presents insights from human breast cancer (HBC) that further support and elucidate the potential relevance of these TME components. As FMCs are highly aggressive tumors, a deeper understanding of their microenvironment could not only improve prognostic accuracy but also uncover novel therapeutic targets. Furthermore, due to their similarities, FMCs offer a potential valuable spontaneous model for HBC, particularly for the aggressive triple-negative phenotypes.