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

• Verfasst von: Safi, Seyer [VerfasserIn]
• Verfasst von: Yamauchi, Yoshikane [VerfasserIn]
• Verfasst von: Eichhorn, Martin E. [VerfasserIn]
• Verfasst von: Warth, Arne [VerfasserIn]
• Verfasst von: Dienemann, Hendrik [VerfasserIn]
• Verfasst von: Hoffmann, Hans [VerfasserIn]
• Titel: Functional T cells targeting tumor-associated antigens are predictive for recurrence-free survival of patients with radically operated non-small cell lung cancer
• Verf.angabe: Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove
• Fussnoten: Published online: 14 Sep 2017 ; Gesehen am 27.06.2018
• Titel Quelle: Enthalten in: OncoImmunology
• Jahr Quelle: 2017
• Band/Heft Quelle: 6(2017,11), Artikel-Nummer e1360458
• ISSN Quelle: 2162-402X
• DOI: doi:10.1080/2162402X.2017.1360458
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1576246671

Abstract

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