Tumor-draining lymph nodes as immunologic hubs: rethinking nodal surgery in the era of checkpoint blockade in urologic cancers

2026-04-01

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Yamamoto, Satoshi *

Higa, Keita

Kurokawa, Koichiro

Bamba, Hiroki

Kanaoka, Sanji

Nakamura, Kazuyoshi

DOI：10.1007/s11255-026-05126-z

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Abstract

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Extended lymph node dissection (LND) is central to curative-intent surgery and pathological staging in urologic oncology, yet randomized trials rarely demonstrate a survival benefit for broader templates, while lymphatic morbidity increases. Tumor-draining lymph nodes (TDLNs) function as immunologic hubs that prime tumor-specific T cells and can sustain immune checkpoint inhibitor (ICI)-responsive progenitor populations, although metastatic TDLNs also develop immunosuppressive dysfunction. This review synthesizes contemporary clinical evidence on LND across major urologic malignancies and integrates these findings with emerging TDLN biology, including progenitor-exhausted CD8(+) T-cell programs and tertiary lymphoid structures relevant to ICI responses. We highlight that the incremental oncologic benefit of extended LND is often modest and disease-specific, whereas pathology-negative regional nodes may contribute to ICI responsiveness by maintaining T-cell reservoirs. Furthermore, we discuss selective nodal strategies-such as sentinel/index node concepts, targeted nodal sampling, and advances in imaging and AI-assisted radiomics-that are intended to preserve staging accuracy and local control, while limiting morbidity and avoiding unselective disruption of potentially immunologically active nodal basins. We conclude that prospective perioperative immunotherapy studies should explicitly evaluate the extent and timing of nodal surgery as biologically relevant variables and incorporate prespecified immune correlates alongside clinical endpoints. Specifically, we propose prospective trial designs that compare upfront standard-template dissection with neoadjuvant ICI followed by response-adapted selective nodal sampling. These studies should incorporate robust clinical endpoints-such as event-free survival and lymphatic morbidity-together with prespecified translational immune correlates, including progenitor-exhausted T-cell dynamics and circulating tumor DNA.

Keywords:

Tumor-draining lymph nodes

Lymph node dissection

Immune checkpoint blockade

Urologic cancers

Tumor microenvironment

Tumor-draining lymph nodes as immunologic hubs: rethinking nodal surgery in the era of checkpoint blockade in urologic cancers

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