ITLN1 suppresses colorectal cancer progression by orchestrating neutrophil maturation and spatial organization
Abstract
Epithelial-derived intelectin-1 (ITLN1) is frequently downregulated in colorectal cancer, but whether it actively shapes anti-tumor immunity remains unclear. We integrate multiplex immunohistochemistry, spatial analysis, single-cell transcriptomics, chromatin-accessibility profiling, and perturbation models to define how ITLN1 regulates neutrophil maturation and spatial anti-tumor immunity. In treatment-naïve human colorectal cancer, higher ITLN1 expression associates with greater neutrophil infiltration, shorter distances between mature S100A9 ⁺ CXCR2 ⁺ neutrophils and ITLN1 ⁺ tumor epithelial cells, and improved survival. In mouse colorectal cancer models, Itln1 silencing accelerates tumor growth and metastasis, impairs CXCR2 ⁺ CD101 ⁺ mature neutrophil generation and tumor recruitment, and promotes LTF ⁺ S100A9 ⁺ immature neutrophil accumulation in hypoxic regions. Mechanistically, ITLN1 activates a JAK1/STAT3-associated C/EBPδ program that drives terminal granulopoiesis and CXCR2-dependent tumor homing, while recombinant ITLN1 restores neutrophil maturation and tumor-killing activity. Here, we reveal a cross-tissue ITLN1–STAT3/C/EBPδ–CXCR2 axis that links epithelial ITLN1 to bone marrow granulopoiesis, coordinating distal neutrophil maturation, mobilization and spatial organization in colorectal cancer.
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BibTeX
@article{chen2026itln1,
title = {{ITLN1 suppresses colorectal cancer progression by orchestrating neutrophil maturation and spatial organization}},
author = {Li Chen and Xiangwei Zhai and Shaoxiang Chen and Jie Luo and Jing Sun and Guibing Qiao and Chen Yang and Yan Zhang and Xiaoying Lou and Meng Kou and Liyan Guo and Ziyue Li and Dan Xie and Zheng Hu and Qizhou Lian},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78599-2},
url = {https://www.nature.com/articles/s41467-026-78599-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ITLN1 suppresses colorectal cancer progression by orchestrating neutrophil maturation and spatial organization
AU - Li Chen
AU - Xiangwei Zhai
AU - Shaoxiang Chen
AU - Jie Luo
AU - Jing Sun
AU - Guibing Qiao
AU - Chen Yang
AU - Yan Zhang
AU - Xiaoying Lou
AU - Meng Kou
AU - Liyan Guo
AU - Ziyue Li
AU - Dan Xie
AU - Zheng Hu
AU - Qizhou Lian
PY - 2026
DA - 2026/10/16
JO - Nature Communications
DO - 10.1038/s41467-026-78599-2
UR - https://www.nature.com/articles/s41467-026-78599-2
AB - Epithelial-derived intelectin-1 (ITLN1) is frequently downregulated in colorectal cancer, but whether it actively shapes anti-tumor immunity remains unclear. We integrate multiplex immunohistochemistry, spatial analysis, single-cell transcriptomics, chromatin-accessibility profiling, and perturbation models to define how ITLN1 regulates neutrophil maturation and spatial anti-tumor immunity. In treatment-naïve human colorectal cancer, higher ITLN1 expression associates with greater neutrophil infiltration, shorter distances between mature S100A9 ⁺ CXCR2 ⁺ neutrophils and ITLN1 ⁺ tumor epithelial cells, and improved survival. In mouse colorectal cancer models, Itln1 silencing accelerates tumor growth and metastasis, impairs CXCR2 ⁺ CD101 ⁺ mature neutrophil generation and tumor recruitment, and promotes LTF ⁺ S100A9 ⁺ immature neutrophil accumulation in hypoxic regions. Mechanistically, ITLN1 activates a JAK1/STAT3-associated C/EBPδ program that drives terminal granulopoiesis and CXCR2-dependent tumor homing, while recombinant ITLN1 restores neutrophil maturation and tumor-killing activity. Here, we reveal a cross-tissue ITLN1–STAT3/C/EBPδ–CXCR2 axis that links epithelial ITLN1 to bone marrow granulopoiesis, coordinating distal neutrophil maturation, mobilization and spatial organization in colorectal cancer.
SN - 2041-1723
ER -