Foxp3(+) regulatory T cells and natural killer cells distinctly infiltrate primary tumors and draining lymph nodes in pulmonary adenocarcinoma.
BACKGROUND
Regulatory T cells (Tregs) can play a key role in suppressing T-cell-mediated immunity in patients with cancer. In this study, the immune cell composition of the lung tissue and draining lymph nodes from patients with non-small cell lung cancer was analyzed.


METHODS
Samples (solid tumor, tumor border, and tumor-free lung tissue, as well as intrapulmonal N1 and mediastinal N2 lymph nodes) from 30 patients subjected to curative resection were analyzed by immunohistochemistry and flow cytometry.


RESULTS
Immunohistochemistry showed the presence of Foxp3(+) Tregs in tumor-infiltrated lung tissue, scattered Tregs in tumor-free lung samples, and a large number of these cells in metastatic lymph nodes. Using flow cytometry, we observed a significant enhancement of CD4(+) T cells and Foxp3(+) Tregs in the tumor center of adenocarcinoma samples, when compared with tumor-free lung tissues and tumor periphery. This enrichment was associated with a drastic decrease in natural killer cell amounts. Metastatic lymph nodes also showed higher Treg numbers than tumor-free ones in patients with lung adenocarcinomas. In contrast, patients with squamous cell carcinomas displayed less profound accumulation of Tregs.


CONCLUSIONS
Accumulation of Tregs in the center of lung tumors and in metastatic lymph nodes in combination with a decrease in the natural killer cell numbers suggests a critical role of Treg in the formation of immunosuppressive tumor microenvironment. Therefore, lung cancer immunotherapy may be improved by a specific Treg elimination or suppression.
Department of Thoracic Surgery, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.
Thomas
T
Schneider
Silvia
S
Kimpfler
Arne
A
Warth
Philipp A
PA
Schnabel
Hendrik
H
Dienemann
Dirk
D
Schadendorf
Hans
H
Hoffmann
Viktor
V
Umansky
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D007124:Immunoenzyme Techniques; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008207:Lymphatic Metastasis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D059016:Tumor Microenvironment
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors