CHARACTERIZATION OF LOCAL AND SYSTEMIC IMMUNOSUPPRESSION IN DOGS WITH MELANOCYTIC NEOPLASMS
immunomodulation; macrophages; melanoma
Tumor evasion mechanisms have been the focus of numerous studies aimed at finding new targets for immunological therapies. Melanomas are immunogenic neoplasms, and the observation of partial or complete regression associated with marked T lymphocyte infiltration supports this assertion. However, this type of neoplasm also exhibits several tumor evasion mechanisms. Furthermore, components of the tumor microenvironment positively or negatively influence neoplasm development. The polarization of M2 macrophages in the inflammatory infiltrate has a pro-tumorigenic effect, as they secrete cytokines with anti-inflammatory action that stimulate local neovascularization. The objective of this study was to characterize local and systemic immunosuppression in dogs diagnosed with melanocytic neoplasia in the Pathological Anatomy Department of the Federal Rural University of Rio de Janeiro (SAP/UFRRJ). Immunohistochemical analyses were performed to determine the number of M2 macrophage subpopulations using anti-CD-206 antibody. These subpopulations may be infiltrated in the neoplasia, regional lymph nodes, and, when obtained at necropsy, other organs (spleen, lung, brain), in addition to the growth fraction or Ki-67 index. Paraffin blocks from the SAP archive were used to study fragments of melanocytic neoplasms in dogs (oral and cutaneous) and their respective regional lymph nodes. For internal organ research, necropsies of previously diagnosed dogs donated for study with informed consent were prioritized. Data were collected on 25 melanocytic neoplasms in dogs, four melanocytomas and the others melanomas. Regarding epidemiology, nine affected females, 16 males, and all animals were adults between seven and 17 years of age. Thirteen cases were located in the skin and 12 in the oral cavity. Among the melanomas, 19 were mixed, four epithelioid, and two spindle-shaped. In 19 of the 25 cases, pleomorphism was moderate to severe, and in 15 cases, more than ten mitotic figures were observed in ten high-power fields (Obj. 40x). Immunohistochemistry with the Ki-67 antibody showed immunoreactivity in 20 cases, all of the malignant variant. A high growth fraction was observed in 13 cases. Seven of these originated in the skin and the other six in the oral cavity. CD206 expression was observed in 21 cases, with intratumoral and peritumoral distribution. Of these, 14 originated in the skin and the other seven in the oral cavity. Thus, it was possible to demonstrate evidence of local and/or systemic alterations and adjustments in dogs with melanocytic neoplasms and establish new prognostic markers, such as CD206, to complement and improve the prognosis of these neoplasms in dogs, as well as to support research in this field in humans.