Tumor-infiltrating lymphocytes and Treg cells in canine melanomas: site-specific prognostic implications

The human melanoma-associated lymphocytic inflammatory infiltrate is considered a prognostic factor; however, this relationship remains poorly established in canine melanomas. Thus, this study aimed to evaluate 117 canine melanomas from different locations (oral cavity/digital - n = 74; cutaneous melanomas - n = 43) using morphological and morphometric analyses of inflammatory cells, CD4+ and FoxP3+ lymphocyte population, and survival rates. Regardless of location, most canine melanomas presented a low frequency of associated inflammatory response. However, when present, the inflammation was discrete, with a focal/multifocal distribution, predominantly lymphocytic, frequent in larger tumors, and associated with higher survival rates. Inflammation was more frequent in oral/digit tumors. Still, it was associated with a milder profile than infiltrates in cutaneous melanomas, with lymphocytes as the predominant cell type and a higher frequency of CD4+ and FoxP3+ cells in more extensive and aggressive tumors. These results indicate that aggressive tumors elicit an immune response, but it is associated with a regulatory profile.