Positioning and reversible suppression of CCR7+ dendritic cells in perivascular tumor niches shape cancer immunity
Tumor-resident CCR7+ dendritic cells (DCs) are key determinants of antitumor T cell responses. Here, we examined the localization of CCR7+ DCs within tumors and the impact of this positioning on antitumor immunity. Spatial, single-cell, and intravital analyses of human cancers and mouse models reveal that CCR7+ DCs form perivascular clusters. Fibroblasts surrounding venous blood vessels produced CCL19, guiding CCR7+ DCs into perivascular niches. Regulatory T (Treg) cells frequently contact perivascular CCR7+ DCs, suppressing CD40 expression and CD4+ and CD8+ T cell activation. Treg cell depletion restored CD40 expression by CCR7+ DCs, enhanced immunostimulatory programs, and improved T cell-dependent tumor control. Anti-PD-1 not only increased perivascular CCR7+ DC clustering and IL-12 production but also strengthened Treg-DC interactions through a CCL22-dependent mechanism, limiting therapeutic efficacy. CCR7+ DCs expressed both co-stimulatory and co-inhibitory molecules, which may underlie their capacity for antitumor activation and concurrent vulnerability to suppression. Modulating the mechanisms that form and restrain CCR7+ DC perivascular immune hubs may improve cancer immunotherapy.
Authors
- Evangelia Bolli (ORCID: https://orcid.org/0000-0002-2012-8314)
- Yuxuan Xie (ORCID: https://orcid.org/0009-0008-0640-2269)
- David Tarussio
- Nagham Alouche (ORCID: https://orcid.org/0000-0002-0695-5612)
- Burkhard Ludewig (ORCID: https://orcid.org/0000-0002-7685-573X)
- Sheri A. C. McDowell (ORCID: https://orcid.org/0000-0002-3155-8547)
- M. Kiss
- Phil F. Cheng (ORCID: https://orcid.org/0000-0003-2940-006X)
- Thorsten R. Mempel (ORCID: https://orcid.org/0000-0001-8635-5424)
- Mehdi Hicham (ORCID: https://orcid.org/0000-0002-9979-4757)
- William C. Faquin (ORCID: https://orcid.org/0000-0002-9043-7171)
- Sanjiv A. Luther (ORCID: https://orcid.org/0000-0002-8758-957X)
- Pratyaksha Wirapati (ORCID: https://orcid.org/0000-0002-0327-4686)
- Chiara Cianciaruso (ORCID: https://orcid.org/0000-0002-5635-5404)
- Jan Hoelzl (ORCID: https://orcid.org/0000-0002-6411-7422)
- Sarah R. Philips (ORCID: https://orcid.org/0000-0003-3197-779X)
- Felix Bayerl (ORCID: https://orcid.org/0000-0002-4737-1808)
- Béatrice Zitti (ORCID: https://orcid.org/0000-0003-4610-7535)
- Julie Terzic (ORCID: https://orcid.org/0000-0002-9464-2041)
- Christopher Garris (ORCID: https://orcid.org/0000-0002-5764-6203)
- Florent Duval
- Dan Celestini
- Ruben Bill
- Tatiana V. Petrova
- Ralph Weissleder
- Giovanni Ciriello
- Olivier Michielin
- Sara I. Pai
- Nawel Zouggari
- Peter M. Sadow
- Stephanie Tissot
- Juhyun Oh
- Thomas Zwahlen
- Jean-Christophe Tille
- Jan P. Böttcher
- Sana Intidhar Labidi-Galy
- Hannah M. Peterson
- Michael Lanuti
- Sergio Quezada
- Philippa Meiser
- Stephanie Hugues
- Marco Varrone
- Paula Nunes-Hasler
- Mari Mino-Kenudson
Publication Details
- Journal
- Open Access CRIS of the University of Bern
- Published
- 2026-01-13
- DOI
- https://doi.org/10.48620/94873
- Primary Topic
- Chemokine receptors and signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00