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

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
DOIs
Publication statusPublished - 9 Nov 2020

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