Unlocking the role of tumor-associated macrophages (TAMs) in feline injection-site sarcomas – a path to immunotherapy

Abstract Feline injection site sarcomas (FISSs) are tumors frequently found at injection sites in domestic cats associated with vaccines and other pharmaceutical substances. The most accepted theory suggests that chronic inflammatory reactions at the injection site trigger these tumors. This study analyzed 58 cases of FISS in cats to investigate the role of tumor-associated macrophages (TAMs). Immunohistochemistry for MAC387+ macrophages was performed via the Novolink™ polymer detection system. TAMs were quantified and categorized into low, moderate, and extensive infiltration groups. Most tumors showed sparse macrophage infiltration (29 out of 58 cases), with moderate macrophage infiltration (18 out of 58), and 11 cases out of 58 showed high infiltration. Significant associations were found between TAM infiltration and the degree of differentiation ( p <0.001), degree of necrosis ( p =0.033), mitotic index ( p = 0.003), and histological degree of malignancy ( p <0.001). This study revealed that TAM density is correlated with tumor aggressiveness in the FISS, suggesting a fundamental role for macrophages in the tumor microenvironment and a promising marker for prognosis.