FOXP3, CD208, and CD206 Expression in Canine Cutaneous Histiocytoma

Canine cutaneous histiocytoma (CCH) is a noninfectious tumor that spontaneously regresses. It is suggested that this regression is due to tumor cell maturation, which is responsible for CD8 lymphocyte activation and tumor cell destruction. Nevertheless, the possible role of the immune microenvironment in tumor regression has not been investigated to date. The aim of this study was to investigate the expression of CD208 and FoxP3 as markers of dendritic cells and regulatory T lymphocytes, respectively, and tumor cell expression of CD206 as a marker of Langerhans cell activation, and relate these parameters to the different phases of CCH and to intratumoral T cell infiltration. Formalin-fixed, paraffin-embedded samples from 31 CCH were evaluated. In each case, the mitotic count and regression phase were recorded. Within the tumor, a quantitative evaluation of immunolabeled CD208⁺ cells, FoxP3⁺ cells, and CD3⁺ lymphocytes was performed, as well as the CD206⁺ tumor cell location. Intratumoral CD208⁺ cells correlated with CD3⁺ lymphocytic infiltration. The possible role of dendritic cells in tumor regression was not confirmed since CD208 seemed to be a nonspecific marker for canine dendritic cells. FoxP3⁺ lymphocyte density was not correlated with any parameter. Neoplastic Langerhans cells presented progressive CD206 expression, from the bottom of the tumor to the epidermis, which correlated with the tumor regression phase and with intratumoral T lymphocyte infiltration. In conclusion, we confirmed a CD206 phenotype change in tumor cells in a spatial group-related pattern, supporting the hypothesis that tumoral Langerhans cells acquire a mature phenotype with tumor regression.