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

•Blood T-cell repertoire alterations and lymphopenia are common in LCNEC patients.•Pretreatment spectratype alterations correlate positively with blood lymphocyte counts.•Both parameters confer better response to treatment and longer survival in LCNEC.•Partial restoration of T-cell repertoire with therapy also predicts longer survival. 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. 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. Untreated stage IV LCNEC patients had significant T-cell repertoire alterations (p