Neoadjuvant chemo-immunotherapy modifies CD4(+)CD25(+) regulatory T cells (Treg) in non-small cell lung cancer (NSCLC) patients.
BACKGROUND
Regulatory 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.


METHODS
The 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.


RESULTS
Treg 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.


CONCLUSIONS
The 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.
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria. Electronic address: andreas.pircher@i-med.ac.at.
Andreas
A
Pircher
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.
Gabriele
G
Gamerith
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.
Arno
A
Amann
Department of General Pathology, Medical University of Innsbruck, Innsbruck, Austria.
Susanne
S
Reinold
Department of General Pathology, Medical University of Innsbruck, Innsbruck, Austria.
Helmut
H
Popper
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.
Anneliese
A
Gächter
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.
Georg
G
Pall
Department of Internal Medicine, St. Vinzenz Krankenhaus Zams, Zams, Austria.
Ewald
E
Wöll
Department of Pneumology, Landeskrankenhaus Natters, Natters, Austria.
Herbert
H
Jamnig
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.
Günther
G
Gastl
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria; Medical Clinic III, Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany.
Anna Maria
AM
Wolf
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.
Wolfgang
W
Hilbe
Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria; Medical Clinic III, Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany. Electronic address: dominik.wolf@ukb.uni-bonn.de.
Dominik
D
Wolf
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007167:Immunotherapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D043823:Taxoids; D000077143:Docetaxel; D000068818:Cetuximab; D002945:Cisplatin
Antibody-induced cellular cytotoxicity (ADCC); Cetuximab; Chemo-immunotherapy; Neoadjuvant therapy; Non-small cell lung cancer (NSCLC); Regulatory T cells (Treg)