Neoadjuvant treatment is associated with fibrotic and transcriptional remodeling of tumor-draining lymph nodes in rectal cancer
Abstract
BackgroundNeoadjuvant treatment is associated with reduced lymph-node yield in rectal cancer, but the accompanying changes in tumor-draining lymph nodes (TDLNs) remain incompletely characterized.MethodsWe analyzed Surveillance, Epidemiology, and End Results data, a 178-patient institutional cohort, quantitative histopathology of 447 histologically negative TDLNs from 159 patients, and bulk RNA sequencing of 30 nodes from 24 patients. Institutional comparisons distinguished a radiotherapy-containing treatment pathway (RT) from management without preoperative radiotherapy (NRT); in the institutional clinical cohort, all 105 RT patients and 10 of 73 NRT patients received neoadjuvant chemotherapy. Pathology models accounted for patient clustering, and RNA counts were aggregated within patients.ResultsRecorded preoperative radiotherapy was associated with lower examined-node counts in Surveillance, Epidemiology, and End Results (SEER). In the institutional cohort, the expanded pretreatment-adjusted incidence-rate ratio was 0.83 [95% confidence interval (CI), 0.67–1.02]; pretreatment-covariate overlap weighting yielded 0.80 (95% CI, 0.66–0.96). RT-group nodes were more fibrotic and smaller, with lower germinal-center and lymphoid-tissue area fractions. Patient-level RNA-seq identified 4,446 differentially expressed genes, with higher extracellular-matrix and angiogenic programs and lower antigen-receptor and B-cell-receptor signaling. Selected pathway directions were retained across sensitivity analyses. Computational deconvolution provided supportive estimates of relative cell composition.ConclusionA radiotherapy-containing neoadjuvant treatment pathway, including chemoradiotherapy in the institutional clinical, pathology, and RNA-seq cohorts, was associated with lower node yield and structural and transcriptional differences in TDLNs. These findings characterize the nodal structural and transcriptional phenotype associated with neoadjuvant treatment.
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BibTeX
@article{shi2026neoadjuvant,
title = {{Neoadjuvant treatment is associated with fibrotic and transcriptional remodeling of tumor-draining lymph nodes in rectal cancer}},
author = {Yihang Shi and Zhixun Zhao and Yuegang Li and Ziwei Cheng and Yaru Niu and Jinzhu Zhang and Hengchang Liu and Shuangmei Zou and Zhen Zhang and Haipeng Chen and Xu Guan and Xishan Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1954681},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1954681},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neoadjuvant treatment is associated with fibrotic and transcriptional remodeling of tumor-draining lymph nodes in rectal cancer
AU - Yihang Shi
AU - Zhixun Zhao
AU - Yuegang Li
AU - Ziwei Cheng
AU - Yaru Niu
AU - Jinzhu Zhang
AU - Hengchang Liu
AU - Shuangmei Zou
AU - Zhen Zhang
AU - Haipeng Chen
AU - Xu Guan
AU - Xishan Wang
PY - 2026
DA - 2026/11/04
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1954681
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1954681
AB - BackgroundNeoadjuvant treatment is associated with reduced lymph-node yield in rectal cancer, but the accompanying changes in tumor-draining lymph nodes (TDLNs) remain incompletely characterized.MethodsWe analyzed Surveillance, Epidemiology, and End Results data, a 178-patient institutional cohort, quantitative histopathology of 447 histologically negative TDLNs from 159 patients, and bulk RNA sequencing of 30 nodes from 24 patients. Institutional comparisons distinguished a radiotherapy-containing treatment pathway (RT) from management without preoperative radiotherapy (NRT); in the institutional clinical cohort, all 105 RT patients and 10 of 73 NRT patients received neoadjuvant chemotherapy. Pathology models accounted for patient clustering, and RNA counts were aggregated within patients.ResultsRecorded preoperative radiotherapy was associated with lower examined-node counts in Surveillance, Epidemiology, and End Results (SEER). In the institutional cohort, the expanded pretreatment-adjusted incidence-rate ratio was 0.83 [95% confidence interval (CI), 0.67–1.02]; pretreatment-covariate overlap weighting yielded 0.80 (95% CI, 0.66–0.96). RT-group nodes were more fibrotic and smaller, with lower germinal-center and lymphoid-tissue area fractions. Patient-level RNA-seq identified 4,446 differentially expressed genes, with higher extracellular-matrix and angiogenic programs and lower antigen-receptor and B-cell-receptor signaling. Selected pathway directions were retained across sensitivity analyses. Computational deconvolution provided supportive estimates of relative cell composition.ConclusionA radiotherapy-containing neoadjuvant treatment pathway, including chemoradiotherapy in the institutional clinical, pathology, and RNA-seq cohorts, was associated with lower node yield and structural and transcriptional differences in TDLNs. These findings characterize the nodal structural and transcriptional phenotype associated with neoadjuvant treatment.
SN - 1664-3224
ER -