title: Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Sophia
authors.initials: S
authors.lastname: Platonova
authors.forename: Julien
authors.initials: J
authors.lastname: Cherfils-Vicini
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
authors.forename: Lucile
authors.initials: L
authors.lastname: Crozet
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.forename: Pascale
authors.initials: P
authors.lastname: André
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.forename: Marco
authors.initials: M
authors.lastname: Alifano
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Régnard
authors.forename: Wolf-Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged