From Metastatic Gateways to Immune Reservoirs: Reframing Tumor-Draining Lymph Nodes in Perioperative Cancer Immunotherapy
Year: 2026
Type: article
Abstract: Immune checkpoint inhibitors (ICIs) are now being introduced into perioperative treatment for several solid tumors. This strategy is usually explained by tumor reduction before surgery or by the elimination of minimal residual disease (MRD) after surgery. However, these explanations may not be sufficient to understand why the timing of ICI treatment, especially before lymph node (LN) removal, is important. In this review, we discuss tumor-draining lymph nodes (tdLNs) from two different aspects. tdLNs are anatomical routes for regional and distant metastasis, but they are also sites where tumor antigens are presented and tumor-specific T cell responses are generated. In particular, tdLNs may maintain stem-like or progenitor-exhausted CD8⁺ T cells, which can respond to PD-1 blockade and give rise to more differentiated exhausted T cells in the tumor. From this viewpoint, neoadjuvant ICI may be effective because the primary tumor, antigen flow, dendritic cell migration, and tdLN-based T cell priming are preserved. We also discuss the possible role of adjuvant ICI in controlling MRD, micrometastases, and metastatic-site draining LNs, and consider future implications for LN surgery and postoperative immune surveillance.
Source: Immuno
Institution: Kindai University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,207
OpenAlex ID: W7170048294