High PD-1 expression on regulatory and effector T-cells in lung cancer draining lymph nodes

Rieneke van de Ven, Anna Larissa N. Niemeijer, Anita G.M. Stam, Sayed M.S. Hashemi, Christian G. Slockers, Johannes M. Daniels, Erik Thunnissen, Egbert F. Smit, Tanja D. de Gruijl, Adrianus J. de Langen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The treatment of advanced nonsmall cell lung cancer (NSCLC) with PD-1/PD-L1 immune checkpoint inhibitors has improved clinical outcome for a proportion of patients. The current challenge is to find better biomarkers than PD-L1 immunohistochemistry (IHC) that will identify patients likely to benefit from this therapy. In this exploratory study we assessed the differences in T-cell subsets and PD-1 expression levels on T-cells in tumour-draining lymph nodes (TDLNs) and peripheral blood mononuclear cells (PBMCs). To evaluate this, flow cytometric analyses were performed on endobronchial ultrasound-guided (EBUS) fine-needle aspirates (FNA) from TDLNs of patients with NSCLC, and the results were compared to paired PBMC samples. For a select number of patients, we were also able to obtain cells from a non-TDLN (NTDLN) sample. Our data show that the frequency of PD-1+ CD4+ and CD8+ T-cells, as well as the PD-1 expression level on activated regulatory T (aTreg) and CD4+ and CD8+ T-cells, are higher in TDLNs than in PBMCs and, in a small sub-analysis, NTDLNs. These elevated PD-1 expression levels in TDLNs may reflect tumour-specific T-cell priming and conditioning, and may serve as a predictive or early-response biomarker during PD-1 checkpoint blockade.

Original languageEnglish
Article number00110-2016
JournalERS Monograph
Volume3
Issue number2
DOIs
Publication statusPublished - 1 Apr 2017

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