Large cell neuroendocrine lung carcinoma induces peripheral T-cell repertoire alterations with predictive and prognostic significance
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...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[May 2018]
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| In: |
Lung cancer
Year: 2018, Volume: 119, Pages: 48-55 |
| ISSN: | 1872-8332 |
| DOI: | 10.1016/j.lungcan.2018.03.002 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.lungcan.2018.03.002 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0169500218302794 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Available online 6 March 2018 Gesehen am 14.05.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1872-8332 |
| DOI: | 10.1016/j.lungcan.2018.03.002 |