Distant lymph nodes compensate for resected tumor-draining lymph nodes during cancer immunotherapy
8 affiliations
- 1Edwin Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA
- 2Edwin Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA; Koch Institute for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- 3Department of Biomedical Engineering, Bucknell University, Lewisburg, PA 17837, USA
- 4Department of Radiation Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- 5Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
- 6Koch Institute for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
- 7Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- 8Edwin Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: [email protected]
Abstract
Surgical removal of tumor-draining lymph nodes (tdLNs) is commonly performed in cancer patients. Here, we investigated whether immune checkpoint blockade (ICB) responses persist after resection of tdLNs, important sites for the initiation and maintenance of anti-cancer immunity. Melanoma patients remained responsive to programmed death 1 (PD-1) blockade after regional LN dissection. Similarly, ICB efficacy persisted after tdLN resection in orthotopic murine melanoma and mammary carcinoma models. Following tdLN removal, interstitial fluid containing soluble antigen was diverted through interstitial spaces across lymphosome boundaries to distant LNs, wherein cancer-derived antigen was acquired and presented to T cells by LN-resident type I conventional dendritic cells. These responses persisted after primary tumor resection and supported ICB-induced systemic immunity. Locoregional delivery of ICB to compensatory LNs enhanced anti-cancer responses after tdLN resection. Consistently, ICB responses in head and neck cancer patients were associated with reactive LNs at distant sites. Thus, antigen rerouting enables distant LNs to compensate for resected tdLNs and sustain anti-cancer immunity, including responses enhanced by immunotherapy.
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BibTeX
@article{menzel2026distant,
title = {{Distant lymph nodes compensate for resected tumor-draining lymph nodes during cancer immunotherapy}},
author = {Lutz Menzel and Hengbo Zhou and James W. Baish and Meghan J. O’Melia and Laurel B. Darragh and Derek N Effiom and Emma Specht and Juliane Czapla and Pin‐Ji Lei and Johanna J. Rajotte and Lingshan Liu and Mohammad R. Nikmaneshi and Mohammad Sayed Razavi and Matthew G. Vander Heiden and Jessalyn M. Ubellacker and Lance L. Munn and Sana D. Karam and Genevieve Marie Boland and Sonia Cohen and Timothy P. Padera},
journal = {Immunity},
year = {2026},
month = oct,
doi = {10.1016/j.immuni.2026.09.009},
url = {https://doi.org/10.1016/j.immuni.2026.09.009},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Distant lymph nodes compensate for resected tumor-draining lymph nodes during cancer immunotherapy
AU - Lutz Menzel
AU - Hengbo Zhou
AU - James W. Baish
AU - Meghan J. O’Melia
AU - Laurel B. Darragh
AU - Derek N Effiom
AU - Emma Specht
AU - Juliane Czapla
AU - Pin‐Ji Lei
AU - Johanna J. Rajotte
AU - Lingshan Liu
AU - Mohammad R. Nikmaneshi
AU - Mohammad Sayed Razavi
AU - Matthew G. Vander Heiden
AU - Jessalyn M. Ubellacker
AU - Lance L. Munn
AU - Sana D. Karam
AU - Genevieve Marie Boland
AU - Sonia Cohen
AU - Timothy P. Padera
PY - 2026
DA - 2026/10/01
JO - Immunity
DO - 10.1016/j.immuni.2026.09.009
UR - https://doi.org/10.1016/j.immuni.2026.09.009
AB - Surgical removal of tumor-draining lymph nodes (tdLNs) is commonly performed in cancer patients. Here, we investigated whether immune checkpoint blockade (ICB) responses persist after resection of tdLNs, important sites for the initiation and maintenance of anti-cancer immunity. Melanoma patients remained responsive to programmed death 1 (PD-1) blockade after regional LN dissection. Similarly, ICB efficacy persisted after tdLN resection in orthotopic murine melanoma and mammary carcinoma models. Following tdLN removal, interstitial fluid containing soluble antigen was diverted through interstitial spaces across lymphosome boundaries to distant LNs, wherein cancer-derived antigen was acquired and presented to T cells by LN-resident type I conventional dendritic cells. These responses persisted after primary tumor resection and supported ICB-induced systemic immunity. Locoregional delivery of ICB to compensatory LNs enhanced anti-cancer responses after tdLN resection. Consistently, ICB responses in head and neck cancer patients were associated with reactive LNs at distant sites. Thus, antigen rerouting enables distant LNs to compensate for resected tdLNs and sustain anti-cancer immunity, including responses enhanced by immunotherapy.
SN - 1074-7613
SN - 1097-4180
ER -