Tumor-draining lymph nodes are pivotal in PD-1/PD-L1 checkpoint therapy

Marieke F. Fransen, Mark Schoonderwoerd, Philipp Knopf, Marcel Gm Camps, Lukas Jac Hawinkels, Manfred Kneilling, Thorbald van Hall, Ferry Ossendorp

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PD-1/PD-L1 checkpoint therapy for cancer is commonly considered to act by reactivating T cells in the tumor microenvironment. Here, we present data from 2 mouse tumor models demonstrating an essential involvement of tumor-draining lymph nodes in PD-1 and PD-L1 therapeutic efficacy. Immune activation induced by checkpoint treatment was predominantly observed in the tumor-draining, but not nondraining, lymph nodes and was reflected in local accumulation of CD8+ T cells. Surgical resection of these lymph nodes, but not contralateral lymph nodes, abolished therapy-induced tumor regressions and was associated with decreased immune infiltrate in the tumor microenvironment. Moreover, inhibitor FTY720, which locks lymphocytes in lymph organs, also abrogated checkpoint therapy, suggesting that the tumor-draining lymph nodes function as sites of T cell invigoration required for checkpoint blockade therapy. Now that PD-1/PD-L1 checkpoint treatment is applied in earlier clinical stages of cancer, our preclinical data advocate for enrolling patients with their tumor-draining lymph nodes still in place, to optimally engage the antitumor immune response and thereby enhance clinical benefit.
Original languageEnglish
JournalJCI Insight
Volume3
Issue number23
DOIs
Publication statusPublished - 2018
Externally publishedYes

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