Functional T cells targeting tumor-associated antigens are predictive for recurrence-free survival of patients with radically operated non-small cell lung cancer

In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immuno...

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Main Authors: Safi, Seyer (Author) , Yamauchi, Yoshikane (Author) , Eichhorn, Martin E. (Author) , Warth, Arne (Author) , Dienemann, Hendrik (Author) , Hoffmann, Hans (Author)
Format: Article (Journal)
Language:English
Published: 2017
In: OncoImmunology
Year: 2017, Volume: 6, Issue: 11
ISSN:2162-402X
DOI:10.1080/2162402X.2017.1360458
Online Access:Verlag, Volltext: http://dx.doi.org/10.1080/2162402X.2017.1360458
Verlag, Volltext: https://doi.org/10.1080/2162402X.2017.1360458
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Author Notes:Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove

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520 |a In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays. We found that circulating TAA-specific T cells were significantly enriched in NSCLC compared with tumor-free patients. The most frequently recognized TAAs were Aurora kinase A, HER2/neu, NY-ESO-1, and p53. TNF-α was the most abundant cytokine secreted by TAA-specific T cells in the blood as well as by in situ-activated tumor-infiltrating lymphocytes, most of which were effector memory cells. The absence of TAA-reactive T cells identified patients at higher risk of tumor recurrence, irrespective of tumor stage (OR = 8.76, 95% CI: 1.57-34.79, p = 0.008). We conclude that pre-existing TAA-reactive circulating T cells are a strong independent prognostic factor for recurrence-free survival. These data may help discriminating high-risk from low-risk patients, improving prognostication, and redirecting adjuvant therapy. Our findings suggest the therapeutic relevance of Aurora kinase A, HER2/neu, NY-ESO-1, and p53 as targets for immunotherapy. This study is registered on Clinicaltrials.gov with trial identification number: NCT02515760 
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