Immune remodeling of breast tumor-draining lymph nodes: antigen-presenting cell dysfunction, regulatory T-cell expansion, and premetastatic niche formation
- 1Department of Breast and Thyroid Surgery, Xiangshan Hospital of Wenzhou Medical University
Abstract
Breast tumor-draining lymph nodes (TDLNs) support antitumor immune priming and frequently harbor the first regional metastases. Pathology-negative nodes can already show impaired dendritic-cell maturation and altered immune-cell positioning, whereas regulatory T-cell expansion becomes more prominent with increasing tumor burden. Lymphatic endothelium, fibroblastic reticular cells, sinus macrophages, and recruited monocytes further regulate antigen access, leukocyte trafficking, and tumor-cell retention. We review human and experimental evidence by nodal stage, breast cancer subtype, and treatment status. We propose a model in which priming competence and support for tumor colonization are related but partly separable dimensions of nodal remodeling. Altered cell positioning may weaken antigen presentation and immune surveillance. Stromal and regulatory feedback may then sustain suppression and favor outgrowth after tumor-cell entry. The order and causal coupling of these events remain unproven in human breast cancer. We distinguish candidate premetastatic alterations, detected before tumor cells at a stated detection limit, from functionally validated niche components that affect subsequent colonization. The model predicts that restoring antigen presentation and limiting stromal support can produce different effects on immune function, initial seeding, and later growth. We propose prospective sampling, antigen-specific functional assays, and timed perturbations to test these predictions and guide stage-specific biomarker development.
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BibTeX
@article{zeng2026immune,
title = {{Immune remodeling of breast tumor-draining lymph nodes: antigen-presenting cell dysfunction, regulatory T-cell expansion, and premetastatic niche formation}},
author = {Liuhai Zeng and Haiyan Wu and Shihang Xue and Minzhi Chen and Jian Song and Wei Lin},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1983258},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983258/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immune remodeling of breast tumor-draining lymph nodes: antigen-presenting cell dysfunction, regulatory T-cell expansion, and premetastatic niche formation
AU - Liuhai Zeng
AU - Haiyan Wu
AU - Shihang Xue
AU - Minzhi Chen
AU - Jian Song
AU - Wei Lin
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1983258
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983258/full
AB - Breast tumor-draining lymph nodes (TDLNs) support antitumor immune priming and frequently harbor the first regional metastases. Pathology-negative nodes can already show impaired dendritic-cell maturation and altered immune-cell positioning, whereas regulatory T-cell expansion becomes more prominent with increasing tumor burden. Lymphatic endothelium, fibroblastic reticular cells, sinus macrophages, and recruited monocytes further regulate antigen access, leukocyte trafficking, and tumor-cell retention. We review human and experimental evidence by nodal stage, breast cancer subtype, and treatment status. We propose a model in which priming competence and support for tumor colonization are related but partly separable dimensions of nodal remodeling. Altered cell positioning may weaken antigen presentation and immune surveillance. Stromal and regulatory feedback may then sustain suppression and favor outgrowth after tumor-cell entry. The order and causal coupling of these events remain unproven in human breast cancer. We distinguish candidate premetastatic alterations, detected before tumor cells at a stated detection limit, from functionally validated niche components that affect subsequent colonization. The model predicts that restoring antigen presentation and limiting stromal support can produce different effects on immune function, initial seeding, and later growth. We propose prospective sampling, antigen-specific functional assays, and timed perturbations to test these predictions and guide stage-specific biomarker development.
SN - 1664-3224
ER -