The PD-1/PD-L1-Checkpoint Restrains T cell Immunity in Tumor-Draining Lymph Nodes

Floris Dammeijer*, Mandy van Gulijk, Evalyn E Mulder, Melanie Lukkes, Larissa Klaase, Thierry van den Bosch, Menno van Nimwegen, Sai Ping Lau, Kitty Latupeirissa, Sjoerd Schetters, Yvette van Kooyk, Louis Boon, Antien Moyaart, Yvonne M Mueller, Peter D Katsikis, Alexander M Eggermont, Heleen Vroman, Ralph Stadhouders, Rudi W Hendriks, Jan von der ThüsenDirk J Grünhagen, Cornelis Verhoef, Thorbald van Hall*, Joachim G Aerts*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

373 Citations (Scopus)

Abstract

PD-1/PD-L1-checkpoint blockade therapy is generally thought to relieve tumor cell-mediated suppression in the tumor microenvironment but PD-L1 is also expressed on non-tumor macrophages and conventional dendritic cells (cDCs). Here we show in mouse tumor models that tumor-draining lymph nodes (TDLNs) are enriched for tumor-specific PD-1+ T cells which closely associate with PD-L1+ cDCs. TDLN-targeted PD-L1-blockade induces enhanced anti-tumor T cell immunity by seeding the tumor site with progenitor-exhausted T cells, resulting in improved tumor control. Moreover, we show that abundant PD-1/PD-L1-interactions in TDLNs of nonmetastatic melanoma patients, but not those in corresponding tumors, associate with early distant disease recurrence. These findings point at a critical role for PD-L1 expression in TDLNs in governing systemic anti-tumor immunity, identifying high-risk patient groups amendable to adjuvant PD-1/PD-L1-blockade therapy.

Original languageEnglish
Pages (from-to)685-700.e8
JournalCancer Cell
Volume38
Issue number5
Early online date1 Oct 2020
DOIs
Publication statusPublished - 9 Nov 2020

Bibliographical note

Copyright © 2020 Elsevier Inc. All rights reserved.

Research programs

  • EMC MGC-02-13-02
  • EMC MM-02-72-02
  • EMC MM-03-24-01
  • EMC MM-04-42-02

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