Characterization of tumor-associated macrophages in canine soft tissue sarcomas reveals histotype-dependent immune microenvironments and correlations with mitotic count and histological grade

Abstract

The tumor-immune microenvironment (TIME) plays a pivotal role in cancer progression, yet its characterization in veterinary oncology remains limited. Eighty-five soft tissue sarcomas (STSs), comprising fibrosarcomas, leiomyosarcomas, liposarcomas, myxosarcomas, and perivascular wall tumors (PWTs), were immunohistochemically assessed for IBA-1 (total tumor-associated macrophages) and CD204 (M2-like macrophages) expression, scored by image analysis, and correlated with histological parameters. IBA-1 was higher in grade 3 STSs compared with grade 1 (W = 3.40, P = .043) and in PWTs compared with myxosarcomas (W = 6.037, P < .001). CD204 was lower in PWTs compared with fibrosarcomas (W = 5.152, P = .003), leiomyosarcomas (W = 4.394, P = .016), and myxosarcomas (W = 4.812, P = .006). Stratifying by STS type, IBA-1 was higher in grade 2 myxosarcomas compared with grade 1 (Mann U = 4, P = .018). IBA-1 and CD204 were higher in myxosarcomas with necrosis compared with those without (Mann U = 5, P = .026, and Mann U = 0, P = .001, respectively). In PWTs, the mitotic count was higher in cases with higher IBA-1 (Spearman’s rho = 0.438, P = .041) and cases with lower CD204 (Spearman’s rho = −0.459, P = .035). Considering all STSs, IBA-1 correlated with total tumor-infiltrating lymphocytes (TILs), T-cells, and regulatory T-cells (Tregs). In fibrosarcomas, IBA-1 and CD204 directly correlated with total TILs, T-cells, and Tregs. In myxosarcomas, CD204 correlated with Tregs. In leiomyosarcomas, IBA-1 scores correlated with Tregs and CD204 with T-cells and Tregs. In PWTs, B-cells correlated with IBA-1 and inversely correlated with CD204. These findings suggest the presence of a TIME favoring anti-tumor immunity in PWTs and a pro-tumoral TIME in myxosarcomas, reinforcing the concept that canine STS histotypes elicit distinct immune responses.