Regional immune zonation of the healthy human ileocolic mucosa and its disruption along the adenoma–carcinoma sequence
Abstract
Colorectal carcinogenesis evolves through a stepwise adenoma–carcinoma sequence accompanied by changes in mucosal immune surveillance. Yet the spatial organisation of healthy ileocolic immunity, and its change during dysplastic progression, remain incompletely defined. We quantified immune cell density (cells/mm²) by compartment-resolved immunohistochemistry for CD3, CD8, CD20, and CD68 with HALO digital image analysis in 820 tissue sections from 57 individuals (14 controls, 16 small [≤ 1 cm] and 17 large [> 1 cm] adenomas, 10 carcinomas). In health, T cells were strongly zonated: enriched in the terminal ileum, decreasing toward the distal colon, and more abundant in stroma than epithelium. This zonation became progressively disrupted across the sequence. Lesional CD3 + density was higher in small than large adenomas. Normal-appearing mucosa showed two additional changes: ileal CD8 + depletion and expansion of right-colonic epithelial CD68 + macrophages. Both followed significant stage-trends. The epithelial CD68 + expansion remained significant after adjustment for age and sex but not after multiplicity correction; the ileal CD8 + change was no longer significant after either adjustment and is hypothesis-generating. These data establish a quantitative reference map of healthy ileocolic immune zonation and suggest that disruption of this spatial organisation, including within normal-appearing mucosa, may represent an early feature of colorectal tumorigenesis.
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BibTeX
@article{valciukiene2026regional,
title = {{Regional immune zonation of the healthy human ileocolic mucosa and its disruption along the adenoma–carcinoma sequence}},
author = {Jurate Valciukiene and Egle Lastauskiene and Aida Laurinaviciene and Matas Jakubauskas and Marius Kryzauskas and Ruta Barbora Valkiuniene and Eugenijus Jasiunas and Renaldas Augulis and Ausra Garnelyte and Ieva Stundiene and Justinas Kavoliunas and Ugne Silinskaite and Tomas Poskus},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-77649-5},
url = {https://www.nature.com/articles/s41598-026-77649-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Regional immune zonation of the healthy human ileocolic mucosa and its disruption along the adenoma–carcinoma sequence
AU - Jurate Valciukiene
AU - Egle Lastauskiene
AU - Aida Laurinaviciene
AU - Matas Jakubauskas
AU - Marius Kryzauskas
AU - Ruta Barbora Valkiuniene
AU - Eugenijus Jasiunas
AU - Renaldas Augulis
AU - Ausra Garnelyte
AU - Ieva Stundiene
AU - Justinas Kavoliunas
AU - Ugne Silinskaite
AU - Tomas Poskus
PY - 2026
DA - 2026/10/27
JO - Scientific Reports
DO - 10.1038/s41598-026-77649-5
UR - https://www.nature.com/articles/s41598-026-77649-5
AB - Colorectal carcinogenesis evolves through a stepwise adenoma–carcinoma sequence accompanied by changes in mucosal immune surveillance. Yet the spatial organisation of healthy ileocolic immunity, and its change during dysplastic progression, remain incompletely defined. We quantified immune cell density (cells/mm²) by compartment-resolved immunohistochemistry for CD3, CD8, CD20, and CD68 with HALO digital image analysis in 820 tissue sections from 57 individuals (14 controls, 16 small [≤ 1 cm] and 17 large [> 1 cm] adenomas, 10 carcinomas). In health, T cells were strongly zonated: enriched in the terminal ileum, decreasing toward the distal colon, and more abundant in stroma than epithelium. This zonation became progressively disrupted across the sequence. Lesional CD3 + density was higher in small than large adenomas. Normal-appearing mucosa showed two additional changes: ileal CD8 + depletion and expansion of right-colonic epithelial CD68 + macrophages. Both followed significant stage-trends. The epithelial CD68 + expansion remained significant after adjustment for age and sex but not after multiplicity correction; the ileal CD8 + change was no longer significant after either adjustment and is hypothesis-generating. These data establish a quantitative reference map of healthy ileocolic immune zonation and suggest that disruption of this spatial organisation, including within normal-appearing mucosa, may represent an early feature of colorectal tumorigenesis.
SN - 2045-2322
ER -