The tumor-sentinel lymph node immuno-migratome reveals CCR7⁺ dendritic cells drive response to sequenced immunoradiotherapy

Robert Saddawi-Konefka (), Riyam Al Msari, Shiqi Tang, Chad Philips, Sayed Sadat, Lauren M. Clubb, Sarah Luna, Santiago Fassardi, Riley Jones, Ida Franiak Pietryga, Farhoud Faraji, Shiruyeh Schokrpur, Bryan S. Yung, Michael M. Allevato, Kelsey E. Decker, Chanond A. Nasamran, Daisy Chilin-Fuentes, Sara Brin Rosenthal, Shawn M. Jensen, Bernard A. Fox, R. Bryan Bell, J. Silvio Gutkind, Andrew Sharabi and Joseph A. Califano ()
Additional contact information
Robert Saddawi-Konefka: UC San Diego School of Medicine
Riyam Al Msari: UC San Diego
Shiqi Tang: UC San Diego
Chad Philips: UC San Diego
Sayed Sadat: UC San Diego
Lauren M. Clubb: UC San Diego
Sarah Luna: UC San Diego
Santiago Fassardi: UC San Diego
Riley Jones: UC San Diego
Ida Franiak Pietryga: UC San Diego
Farhoud Faraji: UC San Diego School of Medicine
Shiruyeh Schokrpur: UC San Diego
Bryan S. Yung: UC San Diego
Michael M. Allevato: UC San Diego
Kelsey E. Decker: UC San Diego
Chanond A. Nasamran: San Diego
Daisy Chilin-Fuentes: San Diego
Sara Brin Rosenthal: San Diego
Shawn M. Jensen: Providence Portland Medical Center
Bernard A. Fox: Providence Portland Medical Center
R. Bryan Bell: Providence Portland Medical Center
J. Silvio Gutkind: UC San Diego
Andrew Sharabi: UC San Diego
Joseph A. Califano: UC San Diego School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Surgical ablation or broad radiation of tumor-draining lymph nodes can eliminate the primary tumor response to immunotherapy, highlighting the crucial role of these nodes in mediating the primary tumor response. Here, we show that immunoradiotherapy efficacy is dependent on treatment sequence and migration of modulated dendritic cells from tumor to sentinel lymph nodes. Using a tamoxifen-inducible reporter paired with CITE-sequencing in a murine model of oral cancer, we comprehensively characterize tumor immune cellular migration through lymphatic channels to sentinel lymph nodes at single-cell resolution, revealing a unique immunologic niche defined by distinct cellular phenotypic and transcriptional profiles. Through a structured approach of sequential immunomodulatory radiotherapy and checkpoint inhibition, we show that sequenced, lymphatic-sparing, tumor-directed radiotherapy followed by PD-1 inhibition achieves complete and durable tumor responses. Mechanistically, this treatment approach enhances migration of activated CCR7+ dendritic cell surveillance across the tumor-sentinel lymph node axis, revealing a shift from their canonical role in promoting tolerance to driving antitumor immunity. Overall, this work supports rationally sequencing immune-sensitizing, lymphatic-preserving, tumor-directed radiotherapy followed by immune checkpoint inhibition to optimize tumor response to immunoradiotherapy by driving activated dendritic cells to draining sentinel lymph nodes.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61780-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61780-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61780-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().