Cigarette Smoke Impairs NK Cell-Dependent Tumor Immune Surveillance

Лу, Л.; Zavitz, Caleb C. J.; Chen, Biao; Kianpour, Sussan; Wan, Yonghong; Stämpfli, Martin R.

doi:10.4049/jimmunol.178.2.936

Cited by 92 publications

(82 citation statements)

References 39 publications

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“…To date, the role of NK cells in the pathogenesis of lung fibrosis remains unclear, and their involvement in this process in the context of autoimmune diseases, including aSS, is not known. Some studies have reported reduced NK cell function in diseases leading to idiopathic pulmonary fibrosis, through the lack of interactions of NK cells with epithelial cells or collagenproducing cells (34,35). Some animal models also suggested that NK cells could prevent lung fibrosis, through the production of IFN-g (36).…”

Section: Discussionmentioning

confidence: 99%

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Hervier

Perez

Allenbach

et al. 2016

The Journal of Immunology

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Antisynthetase syndrome (aSS) is characterized by the association of interstitial lung disease and myositis with anti–tRNA synthetase autoantibodies. Immune mechanisms leading to aSS could be initiated in the lungs, but the role of NK cells has not yet been studied. Both extensive NK cell phenotype and functions were compared between 33 patients and 26 controls. Direct and redirected polyfunctionality assays (degranulation and intracellular production of TNF-α and IFN-γ) were performed spontaneously or after IL-12 plus IL-18 stimulation in the presence of K562 or P815 target cells, respectively. NK cells from inactive patients showed normal phenotype, whereas active aSS revealed a differentiated NK cell profile, as indicated by increased CD57 and Ig-like transcript 2 and an inability to produce IFN-γ (p = 0.002) compared with controls. Importantly, active aSS was more specifically associated with a significant NKp30 decrease (p = 0.009), although levels of mRNA and intracellular protein were similar in aSS and healthy controls. This NKp30 decrease was strongly correlated with reduced NK cell polyfunctionality in both direct and redirected killing assays with anti-NKp30 Abs (p = 0.009 and p = 0.03, respectively), confirming its important impact in aSS. Histological studies revealed massive infiltrations of NK cells inside the lungs of aSS patients (148 versus 11/mm2). Taken together, these data suggest that NK cells and NKp30 could play a role in aSS pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Hervier

Perez

Allenbach

et al. 2016

The Journal of Immunology

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“…It has also been suggested that CS may impair NK cell function, leading to enhanced tumor burden following tumor challenge (58). Unfortunately, this report relied on the use of heterogeneous cell populations, so the contribution of NK cells remains undefined (58). The limited knowledge on NK cell function in COPD and the apparent dichotomy of results further highlight the need for more studies.…”

Section: Discussionmentioning

confidence: 99%

“…The only report directly examining NK cell function in COPD used cells derived from patients using inhaled steroids (56), a variable known to impair functional assays, particularly in COPD (57). It has also been suggested that CS may impair NK cell function, leading to enhanced tumor burden following tumor challenge (58). Unfortunately, this report relied on the use of heterogeneous cell populations, so the contribution of NK cells remains undefined (58).…”

Section: Discussionmentioning

confidence: 99%

Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

Motz¹,

Eppert²,

Wortham³

et al. 2010

The Journal of Immunology

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Chronic obstructive pulmonary disease (COPD) is a debilitating, progressive lung disease punctuated by exacerbations of symptoms. COPD exacerbations are most often associated with viral infections, and exposure to cigarette smoke (CS) followed by viral infection has been shown experimentally to enhance lung inflammation, tissue destruction, and airway fibrosis. Despite this, however, the cellular mechanisms responsible for this effect are unknown. In this study, we examined NK cell function in a mouse model of COPD given the vital role of NK cells following viral infection. Ex vivo stimulation of lung leukocytes with poly(I:C), ssRNA40, or ODN1826 enhanced production of NK cell-derived IFN-γ in CS-exposed mice. NK cells from CS-exposed mice exhibited a novel form of priming; highly purified NK cells from CS-exposed mice, relative to NK cells from filtered air-exposed mice, produced more IFN-γ following stimulation with IL-12, IL-18, or both. Further, NK cell priming was lost following smoking cessation. NKG2D stimulation through overexpression of Raet1 on the lung epithelium primed NK cell responsiveness to poly(I:C), ssRNA40, or ODN1826 stimulation, but not cytokine stimulation. In addition, NK cells from CS-exposed mice expressed more cell surface CD107a upon stimulation, demonstrating that the NK cell degranulation response was also primed. Together, these results reveal a novel mechanism of activation of the innate immune system and highlight NK cells as important cellular targets in controlling COPD exacerbations.

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“…Thus, the definition of a healthy smoker refers to an asymptomatic smoker with normal lung function values, even if respiratory bronchiolitis is present. Oxidative stress, increased epithelial apoptosis and deregulated immune responses represent well known smoking induced mechanisms [14][15][16][17][18][19][20][21]. It is known that cigarette smoking causes inflammatory cell recruitment, mostly macrophages, which have reduced apoptosis and increased survival.…”

Section: Is Smoking Related To the Pathogenesis Of Ilds?mentioning

confidence: 99%

Smoking and interstitial lung diseases

et al. 2015

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For many years has been well known that smoking could cause lung damage. Chronic obstructive pulmonary disease and lung cancer have been the two most common smoking-related lung diseases. In the recent years, attention has also focused on the role of smoking in the development of interstitial lung diseases (ILDs). Indeed, there are three diseases, namely respiratory bronchiolitisassociated ILD, desquamative interstitial pneumonia and pulmonary Langerhans cell histiocytosis, that are currently considered aetiologically linked to smoking and a few others which are more likely to develop in smokers. Here, we aim to focus on the most recent findings regarding the role of smoking in the pathogenesis and clinical behaviour of ILDs. @ERSpublications Smoking is implicated in the pathogenesis and clinical behaviour of interstitial lung disease

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Cigarette Smoke Impairs NK Cell-Dependent Tumor Immune Surveillance

Cited by 92 publications

References 39 publications

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

Smoking and interstitial lung diseases

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