Natural killer cells in inflammatory autoimmune diseases

Yang, Yuyan; Day, Jessica; Guimaraes, Fernando Souza-Fonseca; Wicks, Ian P.; Louis, Cynthia

doi:10.1002/cti2.1250

Cited by 39 publications

(69 citation statements)

References 184 publications

(304 reference statements)

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“…Our data, observing a particular decrease of peripheral cytotoxic NK cells, supports the view of NK cell infiltration to inflamed tissue. This notion is further supported by previous observations of the considerably increased NK cell numbers in the lungs of ASyS patients with PA compared to non-diseased controls [18,19,36].…”

Section: Discussionsupporting

confidence: 84%

“…Importantly, we previously reported a substantially increased numbers of NK cells in the lungs of ASyS patients with PA [18]. Similarly, reduced levels of NK cells in peripheral blood were related to a higher disease activity in DM [20,21], possibly as a result of an increased migration of NK cells into target tissues, such as muscles or the lungs [19]. Altered phenotypes of NK cells, with changed levels of cell-surface receptors, were observed in ASyS, pointing towards shared mechanisms driving autoimmunity in IIM [18].…”

Section: Introductionmentioning

confidence: 86%

“…Such enzymes are immunogenic, including an enhanced interaction with cytokines, as well as a chemoattractant potential to recruit and activate further immune cells [15,17]. NK cells orchestrate the extent of inflammatory the response using the cytolytic properties in IIM capable of inducing bystander self-tissue damage [14,18,19]. Importantly, we previously reported a substantially increased numbers of NK cells in the lungs of ASyS patients with PA [18].…”

Section: Introductionmentioning

confidence: 99%

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NK Cell Patterns in Idiopathic Inflammatory Myopathies with Pulmonary Affection

Pawlitzki

Nelke

Rolfes

et al. 2021

Cells

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Background: Pulmonary affection (PA) is associated with a substantial increase in morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). However, the underlying immune mechanisms of PA remain enigmatic and prompt deeper immunological analyses. Importantly, the Janus-faced role of natural killer (NK) cells, capable of pro-inflammatory as well as regulatory effects, might be of interest for the pathophysiologic understanding of PA in IIM. Methods: To extend our understanding of immunological alterations in IIM patients with PA, we compared the signatures of NK cells in peripheral blood using multi-color flow cytometry in IIM patients with (n = 12, of which anti-synthetase syndrome = 8 and dermatomyositis = 4) or without PA (n = 12). Results: We did not observe any significant differences for B cells, CD4, and CD8 T cells, while total NK cell numbers in IIM patients with PA were reduced compared to non-PA patients. NK cell alterations were driven by a particular decrease of CD56dim NK cells, while CD56bright NK cells remained unchanged. Comparisons of the cell surface expression of a large panel of NK receptors revealed an increased mean fluorescence intensity of NKG2D+ on NK cells from patients with PA compared with non-PA patients, especially on the CD56dim subset. NKG2D+ and NKp46+ cell surface levels were associated with reduced vital capacity, serving as a surrogate marker for clinical severity of PA. Conclusion: Our data illustrate that PA in IIM is associated with alterations of the NK cell repertoire, suggesting a relevant contribution of NK cells in certain IIMs, which might pave the way for NK cell-targeted therapeutic approaches.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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NK Cell Patterns in Idiopathic Inflammatory Myopathies with Pulmonary Affection

Pawlitzki

Nelke

Rolfes

et al. 2021

Cells

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“…Beyond B and T cells, NK cells have a role stimulating or suppressing autoimmunity. 59 The NKs profile of the lungs is very similar to that found in peripheral blood, 60 and although there are no data on NKs association with irAEs, elevated levels of NKs have been described in the lungs of patients with hypersensitivity Pn or organizing pneumonitis not related to anti-PD(L)-1 treatment. 61 …”

Section: Discussionmentioning

confidence: 70%

Clinical and molecular parameters associated to pneumonitis development in non-small-cell lung cancer patients receiving chemoimmunotherapy from NADIM trial

Sierra-Rodero

Cruz-Bermúdez

Nadal

et al. 2021

J Immunother Cancer

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BackgroundPneumonitis (Pn) is one of the main immune-related adverse effects, having a special importance in lung cancer, since they share affected tissue. Despite its clinical relevance, Pn development remains an unpredictable treatment adverse effect, whose mechanisms are mainly unknown, being even more obscure when it is associated to chemoimmunotherapy.MethodsIn order to identify parameters associated to treatment related Pn, we analyzed clinical variables and molecular parameters from 46 patients with potentially resectable stage IIIA non-small-cell lung cancer treated with neoadjuvant chemoimmunotherapy included in the NADIM clinical trial (NCT03081689). Pn was defined as clinical or radiographic evidence of lung inflammation without alternative diagnoses, from treatment initiation to 180 days.ResultsAmong 46 patients, 12 developed Pn (26.1%). Sex, age, smoking status, packs-year, histological subtype, clinical or pathological response, progression-free survival, overall survival and number of nivolumab cycles, were not associated to Pn development. Regarding molecular parameters at diagnosis, Pn development was not associated to programmed death ligand 1, TPS, T cell receptor repertoire parameters, or tumor mutational burden. However, patients who developed Pn had statistically significant lower blood median levels of platelet to monocyte ratio (p=0.012) and teratocarcinoma-derived growth factor 1 (p=0.013; area under the curve (AUC) 0.801), but higher median percentages of natural killers (NKs) (p=0.019; AUC 0.786), monocytes (p=0.017; AUC 0.791), MSP (p=0.006; AUC 0.838), PARN (p=0.017; AUC 0.790), and E-Cadherin (p=0.022; AUC 0.788). In addition, the immune scenario of Pn after neoadjuvant treatment involves: high levels of neutrophils and NK cells, but low levels of B and T cells in peripheral blood; increased clonality of intratumoral T cells; and elevated plasma levels of several growth factors (EGF, HGF, VEGF, ANG-1, PDGF, NGF, and NT4) and inflammatory cytokines (MIF, CCL16, neutrophil gelatinase-associated lipocalin, BMP-4, and u-PAR).ConclusionsAlthough statistically underpowered, our results shed light on the possible mechanisms behind Pn development, involving innate and adaptative immunity, and open the possibility to predict patients at high risk. If confirmed, this may allow the personalization of both, the surveillance strategy and the therapeutic approaches to manage Pn in patients receiving chemoimmunotherapy.

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“…20 These aspects, and the potential mechanisms and participation of NK cells in other inflammatory autoimmune diseases, are discussed in depth in the review by Yang and colleagues to conclude this CTI Special Feature. 21 The role of NK cells in autoimmune inflammatory disorders is an important factor, as over-activation or enhancing of NK cell effector functions should be taken into consideration in the context of NK cell-targeted therapeutics, such as the treatment of cancer patients who concomitantly suffer from rheumatoid disease.…”

mentioning

confidence: 99%