Background: CD163 is a scavenger receptor predominantly expressed on the surfaces of macrophages in various mammalian species and is a marker of anti-inflammatory (M2-like) macrophages. High density of CD163-positive tumor-associated macrophages (TAMs) is associated with worse prognosis in various patient tumors. Interestingly, studies on mice have shown that CD163-positive TAMs only infiltrate the margins of tumor tissues, not the center. Based on these observations, we hypothesized that circulating monocyte-derived macrophages (MDMs), which are the origin of most TAMs, do not express CD163 in mice.
Results: We examined CD163 expression in MDMs, differentiated from healthy animals in vitro, and in normal, pathogenic, and tumorigenic macrophages infiltrating various tumors and organs across multiple species including primates, rodents, cetartiodactylans, and carnivores. We found that MDMs, including TAMs, do not express CD163 in mice. Our findings also suggest that murine CD163-positive macrophages likely originate from a specific subset of resident macrophages, namely fetal liver monocytes/macrophages, as indicated by fetal analysis. Furthermore, we revealed that the CD163-negative expression pattern in MDMs is a trait shared by the rodent clade.
Conclusions: Rodent MDMs do not express CD163, a phenotype not shared with MDMs of other mammals. Our findings caution against the extrapolation of rodent experimental results to other animal models.
Keywords: Kupffer cell; fetal liver; resident macrophage; tumor‐associated macrophage; yolk sac.
© 2025 The Author(s). Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.