Relationship between the inflammatory tumor microenvironment and different histologic types of canine mammary tumors

Abstract

Mammary neoplasms are the tumors with higher incidence in female dogs. Among the factors that contribute for the development of this and other neoplasms, the inflammatory tumor microenvironment plays a crucial role. Several studies reported important roles for lymphocytes, macrophages, plasma cells, neutrophils, eosinophils and mast cells in this context. In the present study, our aim was to evaluate the number of profile cells of inflammatory cells and area of tumor fibrosis and the relation of these features with canine mammary tumors of different histologic and clinical presentation (benign mixed tumor, carcinoma in mixed tumor, solid carcinoma and tubular carcinoma) Counting and staining of inflammatory cells and tumor fibrosis were performed through histochemistry, while counting and staining of CD4, TCD8 and FOXP3 lymphocytes were performed through immunohistochemistry. Statistical analysis of the association between densities of inflammatory cells, tumor fibrosis and histologic types revealed significant difference for plasma cells (p = .035), neutrophils (p = .0113), macrophages (p = .0047), and tumor fibrosis (p = .05). The found data suggest associations between high number of neutrophils and aggressive mammary tumors, between high densities of plasma cells, macrophages and CD8 cells and between low number of profile cells of CD4 cells and less aggressive tumors. Larger areas of tumor fibrosis showed relation to more aggressive canine mammary tumors.

Know Thy Model: Charting Molecular Homology in Stromal Reprogramming Between Canine and Human Mammary Tumors

“…More detailed assessment of the localization of immune infiltrates with respect to the tumor cells found that tumor-infiltrating CD3+ T-lymphocytes were significantly more frequent in benign than malignant tumors, and conversely, peripheral CD3+ cells were more frequent in malignant than benign tumors (Carvalho et al, 2011). Furthermore, high number of neutrophils were associated with aggressive CMTs, while in contrast high amounts of plasma cells, macrophages, and CD8+ T-cells, together with low numbers of CD4+ T-cells, were associated with less aggressive tumors (de Souza et al, 2018). Taken together, these results suggest a strong role for T-lymphocytes in progression of CMTs, and also highlight that it is important to assess not only abundance of immune cells, but also identify their subtypes and define their exact localization within the tumor, as infiltrating immune cells that shielded from reaching the tumor cells cannot achieve immune control, and might really do more damage by fueling tumor-promoting inflammation instead.…”

Tumor–Microenvironment Interaction: Analysis of Mast Cell Populations in Normal Tissue and Proliferative Disorders of the Canine Prostate

“…Recent studies in human and veterinary medicine have focused on the interactions between tumor cells and the surrounding microenvironment, in order to better describe the characteristics of cancer [1,2,3,4,5,6]. Tumor microenvironment is an evolving concept that defines the behavior of cancer not only by the study of tumor cells alone, but also in association with the surrounding background that tumor cells need for survival, growth, proliferation and metastatic spread [7].…”

The Expression of Selected Factors Related to T Lymphocyte Activity in Canine Mammary Tumors

“…Multiple studies have demonstrated the presence of T lymphocytes in various types of mammary gland neoplasms [19]. A recent study has shown that lymphocytes comprise the primary population of inflammatory cells infiltrating mammary tumors regardless of their histological type [6]. Moreover, several studies have shown that a high number of infiltrating CD3 + T cells is associated with poor prognoses and lower survival rates [14,18,44].…”

“…Tumor-associated macrophages (TAMs) also play an important role in canine mammary cancer development [6,8]. They are different from monocytes, which are actively recruited from bone marrow by cancer cells.…”