Distant lymph nodes compensate for resected tumor-draining lymph nodes during cancer immunotherapy

Authors

• Lutz Menzel, Massachusetts General Hospital
• Hengbo Zhou, Massachusetts General Hospital
• James W. Baish, Bucknell UniversityFollow
• Meghan O'Melia, Massachusetts General Hospital
• Laurel B. Darragh, Univesity of Colorado Anschutz Medical Campus
• Derek N. Effiom, Massachusetts General Hospital
• Emma Sprecht, Massachusetts General Hospital
• Juliane Czapla, Massachusetts General Hospital
• Pin-Ji Lei, Massachusetts General Hospital
• Johanna Rajotte, Massachusetts General Hospital
• Lingshan Liu, Massachusetts General Hospital
• Mohammad R. Nikmaneshi, Massachusetts General Hospital
• Mohammad Razavi, Massachusetts General Hospital
• Matthew Vander Heidem, MIT
• Jessalyn Ubellacker, Harvard University
• Lance Munn, Massachusetts General Hospital
• Sana D. Karam, University of Colorado Anshutz Medical Campus
• Genevieve Boland, Massachusetts General Hospital
• Sonia Cohen, Massachusetts General Hospital
• Timothy Padera, Massachusetts General Hospital

Publication Date

10-13-2026

Description

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.

Journal

Immunity

Volume

59

First Page

2808

Last Page

2823

Department

Biomedical Engineering

Link to Published Version

https://www.cell.com/immunity/fulltext/S1074-7613(26)00384-5

DOI

10.1016/j.immuni.2026.09.009

Recommended Citation

Lutz Menzel, Hengbo Zhou, James W. Baish, Meghan J. O’Melia, Laurel B. Darragh, Derek N. Effiom, Emma Specht, Juliane Czapla, Pin-ji Lei, Johanna J. Rajotte, Lingshan Liu, Mohammad R. Nikmaneshi, Mohammad S. Razavi, Matthew G. Vander Heiden, Jessalyn M. Ubellacker, Lance L. Munn, Sana D. Karam, Genevieve M. Boland, Sonia Cohen, Timothy P. Padera, Distant lymph nodes compensate for resected tumor-draining lymph nodes during cancer immunotherapy, Immunity, Volume 59, Issue 10, 2026, Pages 2808-2823.e9, ISSN 1074-7613, https://doi.org/10.1016/j.immuni.2026.09.009. https://www.sciencedirect.com/science/article/pii/S1074761326003845