What We Know and Do Not Yet Know About the Canine Model of Lymphoma in Human Medicine-The Current State of Knowledge.

This review comprehensively compares lymphoma in humans and dogs, highlighting the canine model's utility in translational research. Canine lymphoma (cL), predominantly diffuse large B-cell lymphoma (DLBCL), mirrors human non-Hodgkin's lymphoma (NHL) in its clinical presentation, including lymphadenopathy, systemic symptoms (e.g., fever, weight loss), and hematological abnormalities. Morphologically, cL and NHL share similarities in DLBCL subtypes (centroblastic, immunoblastic, anaplastic), although some variations exist, such as the presence of macronuclear medium-sized cells in canine polymorphonuclear centroblastic lymphoma, not observed in humans. Canine and human lymphomas share molecular mechanisms, including the activation of key pathways like NF-κB and mTOR, and genetic and epigenetic alterations. The tumor microenvironment influences tumor growth and immune evasion in both species. Both species exhibit similar responses to chemotherapy, primarily CHOP-based protocols, although canine lymphoma often progresses more rapidly, offering advantages for shorter clinical trials. Molecular targeted therapy is emerging as a promising treatment, with human therapies like rituximab and chimeric antigen receptor T-cell therapy showing efficacy, and canine treatments still developing. Epidemiological data reveal overlapping risk factors, including exposure to environmental carcinogens (e.g., household chemicals, pollution) and the potential influence of sex hormones, although the role of sex hormones requires further investigation in canines. While staging systems differ slightly (Lugano modification of Ann Arbor for humans, WHO system for dogs), both consider disease extent and systemic involvement. Prognostic factors, such as lactate dehydrogenase (LDH) levels, are relevant in human NHL but have not shown consistent utility in cL. This study concludes that the spontaneous development of cL in immunocompetent dogs, coupled with its clinical, histological, and therapeutic similarities to human NHL, makes the canine model invaluable for preclinical research, accelerating the development of novel diagnostic tools and therapies for both human and canine lymphoma. The shared environmental risk factors and shorter disease progression in dogs further enhance the translational potential of this model, promoting a One Health approach to cancer research.