Large cell neuroendocrine lung carcinoma induces peripheral T-cell repertoire alterations with predictive and prognostic significance

• Verfasst von: Christopoulos, Petros [VerfasserIn]
• Verfasst von: Schneider, Marc [VerfasserIn]
• Verfasst von: Bozorgmehr, Farastuk [VerfasserIn]
• Verfasst von: Kuon, Jonas [VerfasserIn]
• Verfasst von: Muley, Thomas [VerfasserIn]
• Verfasst von: Bischoff, Helge [VerfasserIn]
• Verfasst von: Thomas, Michael [VerfasserIn]
• Verfasst von: Meister, Michael [VerfasserIn]
• Titel: Large cell neuroendocrine lung carcinoma induces peripheral T-cell repertoire alterations with predictive and prognostic significance
• Verf.angabe: Petros Christopoulos, Marc A. Schneider, Farastuk Bozorgmehr, Jonas Kuon, Walburga Engel-Riedel, Jens Kollmeier, Volker Baum, Thomas Muley, Philipp A. Schnabel, Helge Bischoff, Christian Grohé, Monika Serke, Michael Thomas, Paul Fisch, Michael Meister
• E-Jahr: 2018
• Jahr: [May 2018]
• Umfang: 8 S.
• Illustrationen: Illustrationen
• Fussnoten: Available online 6 March 2018 ; Gesehen am 14.05.2019
• Titel Quelle: Enthalten in: Lung cancer
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1985
• Jahr Quelle: 2018
• Band/Heft Quelle: 119(2018), Seite 48-55
• ISSN Quelle: 1872-8332
• DOI: doi:10.1016/j.lungcan.2018.03.002
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Immune status
• Sach-SW: Large cell neuroendocrine lung carcinoma
• Sach-SW: Lymphopenia
• Sach-SW: Prognosis
• Sach-SW: Spectratyping
• Sach-SW: T-cell repertoire
• K10plus-PPN: 1665494530

Abstract

Objectives - This study was performed to evaluate for a potentially important role of T cells in the pathophysiology and treatment sensitivity of large cell neuroendocrine lung carcinoma (LCNEC), an orphan disease with poor prognosis and scarce data to guide novel therapeutic strategies. - Materials and methods - We performed T-cell receptor (TCR) β-chain spectratyping on blood samples of patients treated within the CRAD001KDE37 trial (n=35) using age-matched current or former (n=11) and never smokers (n=10) as controls. The data were analyzed in conjunction with the complete blood counts of the probands as well as the data about response to treatment and overall survival in the clinical trial. - Results and conclusion - Untreated stage IV LCNEC patients had significant T-cell repertoire alterations (p<0.001) compared to age-matched smokers. These changes correlated positively with blood lymphocyte counts (r=0.49, p<0.01), suggesting antigen-induced T-cell proliferation as the causative mechanism. At the same time, LCNEC patients showed mild lymphopenia (1.54 vs. 2.51/nl in median, p<0.01), which reveals a second, antigen-independent mechanism of systemic immune dysregulation. More pronounced T-cell repertoire alterations and higher blood lymphocyte counts at diagnosis were associated with a better treatment response by RECIST and with a longer overall survival (441 vs. 157days in median, p=0.019). A higher degree of T-cell repertoire normalization after 3 months of therapy also distinguished a patient group with more favourable prognosis (median overall survival 617 vs. 316days, p=0.036) independent of radiological response. Thus, LCNEC induces clinically relevant changes of the T-cell repertoire, which are measurable in the blood and could be exploited for prognostic, predictive and therapeutic purposes. Their pathogenesis appears to involve antigen-induced oligoclonal T-cell expansions superimposed on TCR-independent lymphopenia.