MICROAMBIENTE STROMALE IN MODELLI SPONTANEI DI PATOLOGIA NEOPLASTICA: NUOVE EVIDENZE NELLA GHIANDOLA MAMMARIA DEL CANE

Mammary tumours are frequently diagnosed in unspayed female dogs. Fifty percent of these tumours are malignant and can be life-threatening. Canine mammary tumours are similar to human breast tumours and are often used as a translational model of breast cancer. The preferred treatment for mammary tumours is mastectomy, which involves significant tissue damage and moderate to intense pain. Several studies have been conducted to ensure effective pain relief during mastectomy, with tumescent anaesthesia showing excellent results. The tumour behaviour is strongly influenced by its surrounding stromal microenvironment. This is constantly changing and involves various immune cells. With the rise of immunotherapy, there is a focus on understanding the connection between cancer and the immune system. Preserving the tumour microenvironment is a challenge when using two-dimensional cell cultures. This has led researchers to seek out three-dimensional culture systems that can mimic the natural tumour environment. This PhD thesis aimed to investigate the possible artifacts related to the subcutaneous inoculation of the analgesic solution for tumour anaesthesia in canine mammary tumours. The research then focused on the tumour microenvironment, particularly examining tumour-infiltrating lymphocytes, tertiary lymphoid structures, and haemosiderin-laden macrophages. Additionally, sections of canine mammary tumour were cultured with PRP to assess the potential of PRP as a medium in histocultures. The results showed that tumescent anaesthesia caused histological artefacts, preventing diagnosable reading of the sample. Analysis of the stromal microenvironment revealed the existence of tertiary lymphoid structures in canine mammary tumours. Furthermore, it was shown that the increase in TILs and the presence of TLSs were closely connected and correlated with higher degree of malignancy. The HLMs were immunohistochemically positive for proangiogenic and protumoural molecules. Histocoltures showed that PRP ensured tissue integrity and immunogenicity. Cell proliferation was also evident. The thesis therefore highlights new evidence on canine mammary tumours that may represent important elements in both human and veterinary medicine.