Spatial Patterns and Prognostic Relevance of CD1a Immature and CD208 Mature Dendritic Cells in Colorectal Cancer From Tumour-adjacent Mucosa to Liver Metastases

Abstract

Background. The prognostic role of dendritic cells (DCs) in colorectal cancer (CRC) and paired livermetastases (LM) remains unclear, particularly regarding the dynamics of immature CD1a+ and matureCD208+ subsets across anatomical compartments and synchronous versus metachronous disease.Patients and methods. This retrospective cohort included patients undergoing resection of primary CRC(pCRC) and synchronous LM (N = 55) or metachronous LM (N = 44). Immunohistochemical staining forCD1a and CD208 was performed on non tumour adjacent normal mucosa (NAM), tumour center (TC),inner and outer invasive margins (IM, OM), and peritumoural tissue (PT). Cell densities were quantifi edon whole-slide images using QuPath software and correlated with overall survival (OS).Results. CD1a+ DCs were nearly absent in NAM but enriched in pCRC TC, whereas CD208+ DCspredominated in NAM lymphoid aggregates and peripheral compartments of pCRC and LM. CD1a+ cellsfollowed a TC/IM > OM/PT gradient, while CD208+ cells showed the opposite, consistent with arecruitment-maturation axis. In synchronous cases, CD1a+ densities were higher in pCRC than LM,supporting the role of the primary tumour as a "monocyte reservoir." Survival analysis revealed that highCD208+ density in TC of synchronous LM (HR = 0.47; p = 0.033) and high CD1a+ density in TC ofmetachronous LM (HR = 0.44; p = 0.050) were both associated with reduced mortality risk.Conclusion. This study provides the fi rst detailed mapping of CD1a+ and CD208+ DCs across NAM, pCRCand paired LM, indicating that their prognostic impact is determined not only by absolute numbers but,more importantly, by compartmental distribution and the timing of metastasis.