• Andreas Pircher, Gabriele Gamerith, Arno Amann, Susanne Reinold, Helmut Popper, Anneliese Gächter, Georg Pall, Ewald Wöll, Herbert Jamnig, Günther Gastl, Anna Maria Wolf, Wolfgang Hilbe, and Dominik Wolf.
• Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria. Electronic address: andreas.pircher@i-med.ac.at.
• Lung Cancer. 2014 Jul 1; 85 (1): 81-7.

BackgroundRegulatory T cells (Treg) are critical for cancer immune evasion; whereas natural killer (NK) cells are central for effective anti-tumor immunity including antibody-induced cellular cytotoxicity (ADCC). The predictive role of Treg levels for clinical response to chemo-immunotherapy in non-small cell lung cancer (NSCLC) as well as therapy-induced Treg changes remain to be defined.Patients And MethodsThe impact of Treg on NK-mediated cetuximab-dependent cellular cytoxicity was tested in vitro. Frequency and functional activity of Treg was analyzed in 31 NSCLC stage IB-IIIA patients treated by neoadjuvant Cetuximab/Docetaxel/Cisplatin prior to surgery. Data were correlated with clinical outcome variables and Treg tumor infiltration.ResultsTreg potently inhibit NK-mediated and cetuximab-induced ADCC in vitro. In addition, a significant correlation between Treg reduction and clinical response was seen. However, the grade of tumor infiltrating Treg in resected tumors did not correlate with peripheral Treg levels. Moreover, Treg levels at diagnosis did not predict clinical response to chemo-immunotherapy.ConclusionsThe drop of Treg levels during neoadjuvant chemo-immunotherapy in NSCLC patients significantly correlates with clinical response. However, Treg at diagnosis are not linked to inferior clinical response to chemo-immunotherapy in NSCLC in vivo even though Treg efficiently inhibit ADCC in vitro.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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