Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma

Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2011-08, Vol.71 (16), p.5412-5422
Main Authors: PLATONOVA, Sophia, CHERFILS-VICINI, Julien, FRIDMAN, Wolf-Herman, SAUTES-FRIDMAN, Catherine, CREMER, Isabelle, DAMOTTE, Diane, CROZET, Lucile, VIEILLARD, Vincent, VALIDIRE, Pierre, ANDRE, Pascale, DIEU-NOSJEAN, Marie-Caroline, ALIFANO, Marco, REGNARD, Jean-François
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic agents
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - immunology
Coculture Techniques
Female
Flow Cytometry
Humans
Immunohistochemistry
Immunophenotyping
K562 Cells
Killer Cells, Natural - immunology
Lung Neoplasms - immunology
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Pneumology
Tumors
Tumors of the respiratory system and mediastinum
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Summary:Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non-small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-γ production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-10-4179