Large cell neuroendocrine lung carcinoma induces peripheral T-cell repertoire alterations with predictive and prognostic significance.
Lung Cancer
; 119: 48-55, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29656752
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 ANDMETHODS:
We performed T-cell receptor (TCR) ß-chain spectratyping on blood samples of patients treated within the CRAD001KDE37 trial (nâ¯=â¯35) using age-matched current or former (nâ¯=â¯11) and never smokers (nâ¯=â¯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 ANDCONCLUSION:
Untreated stage IV LCNEC patients had significant T-cell repertoire alterations (pâ¯<â¯0.001) compared to age-matched smokers. These changes correlated positively with blood lymphocyte counts (râ¯=â¯0.49, pâ¯<â¯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, pâ¯<â¯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. 157â¯days in median, pâ¯=â¯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. 316â¯days, pâ¯=â¯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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Carcinoma Neuroendócrino
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Carcinoma de Células Grandes
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Genes Codificadores da Cadeia beta de Receptores de Linfócitos T
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Neoplasias Pulmonares
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article