Spatial Profiling and Prognostic Role of CD169+ Macrophages in Colorectal Cancer From Adjacent Nontumor Mucosa to Liver Metastasis

Abstract

BACKGROUND: CD169+ cells represent a distinct subset of macrophages with potential immunomodulatory roles, but their function in colorectal cancer (CRC) progression remains unclear. This study focuses on the spatial profiling and prognostic significance of CD169+ macrophages in adjacent nontumor mucosa (NM), primary CRC (pCRC), and synchronous or metachronous liver metastases (LM). MATERIALS AND METHODS: We enrolled into this retrospective cohort study patients who underwent resection of both pCRC with adjacent NM and synchronous LM (N = 55) or metachronous LM (N = 44). We applied immunohistochemical staining and computer-assisted image analysis to quantify CD169+ cell density in the NM, pCRC, synchronous, and metachronous LM. Correlations between CD169+ macrophages and T cells were evaluated. Associations between CD169+ cell density and overall survival (OS) of the patients were assessed. RESULTS: CD169+ cell density was greater in NM than in the tumor center (TC) of pCRC and in the peritumor (PT) region of LM compared to pCRC. The synchronous group exhibited a higher density of CD169+ cells than the metachronous group in the inner margin (IM) of pCRC, the TC, and the outer margin (OM) of LM. CD169+ cells were more abundant in the exterior than in the interior tumor areas in both pCRC and LM. Positive correlations were observed between densities of CD169+ macrophages with CD3+ and CD8+ lymphocytes. In the synchronous group, a high density of CD169+ macrophages in the TC of pCRC was associated with longer OS, whereas a high density in the PT of LM was associated with shorter OS. High density of CD169+ macrophages in the OM of metachronous LM was associated with poor survival. CONCLUSION: Our study highlights context-dependent prognostic associations of CD169+ macrophages in CRC. While high CD169+ macrophage density in the TC of pCRC was linked to favorable survival in the synchronous group, increased density in both synchronous and metachronous LM was associated with adverse outcomes. Further prospective studies and functional investigations are needed to validate these observations.