Characterization of the Tumor Microenvironment in Feline Injection-Site Sarcomas: The Role of TAMs and CAFs

Background: Feline injection-site sarcomas (FISS) are aggressive mesenchymal tumors arising from chronic post-injection inflammation. This review investigates how tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) influence the FISS tumor microenvironment (TME) and which biomarkers including PD-(L)۱, cyclooxygenase-۲ (COX-۲), matrix metalloproteinases (MMPs), and fibroblast activation protein (FAP), associate with aggressiveness and therapeutic potential. Methods: This narrative review followed PRISMA ۲۰۲۰ guidelines. Studies published between ۲۰۰۰ and ۲۰۲۵ were retrieved from PubMed, Scopus, Web of Science, and Google Scholar using terms linking “feline injection-site sarcoma” with “TAMs”, “CAFs”, “PD-L۱”, “COX-۲”, and “MMPs”. Eligible feline studies describing histological or molecular TME features were analyzed to identify key biomarkers and pathogenic trends. Results: FISS is characterized by macrophage-rich, inflammatory stroma with frequent PD-(L)۱ and COX-۲ expression, elevated MMP-۲/-۹ activity, and angiogenesis paralleling proliferation. FAP-positive CAFs, identified in feline soft tissue sarcomas, likely cooperate with TAM-driven immunosuppression to enhance invasion and recurrence. Conclusion: Despite limited cohort sizes and methodological variability, evidence highlights TAMs and CAFs as central drivers of FISS progression. Integrating wide excision ± radiotherapy with biomarker-guided adjuncts, targeting checkpoint, COX-۲, matrix, and FAP pathways, represents a rational, TME-informed approach to improve outcomes in feline oncology.

کلیدواژه ها:

feline injection-site sarcoma ، tumor-associated macrophages ، cancer-associated fibroblasts ، immunohistochemistry ، immune checkpoint