TY - JOUR
T1 - High PD-1 expression on regulatory and effector T-cells in lung cancer draining lymph nodes
AU - van de Ven, Rieneke
AU - Niemeijer, Anna-Larissa N.
AU - Stam, Anita G. M.
AU - Hashemi, Sayed M. S.
AU - Slockers, Christian G.
AU - Daniels, Johannes M.
AU - Thunnissen, Erik
AU - Smit, Egbert F.
AU - de Gruijl, Tanja D.
AU - de Langen, Adrianus J.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85081950648&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/28560238
U2 - https://doi.org/10.1183/23120541.00110-2016
DO - https://doi.org/10.1183/23120541.00110-2016
M3 - Article
C2 - 28560238
SN - 2312-508X
VL - 3
JO - ERS Monograph
JF - ERS Monograph
IS - 2
M1 - 00110-2016
ER -