Shaping of NK cell subsets by aging

Solana, Rafael; Campos, Carmen; Pera, Alejandra; Tarazona, Raquel

doi:10.1016/j.coi.2014.04.002

Cited by 132 publications

(99 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The mean age of HCC patients included in the present study was significantly older compared to controls (both normal volunteers and cirrhotic patients with chronic HCV infection). However, this feature is likely unrelated to the differences detected in NK-cell phenotype, since the NK-cell population in the elderly appears to be characterized by a reduction of CD56 BR NK-cells, of NKp30 and NKp46 expression 17 with unchanged expression of NKG2A and perforin compared to younger individuals. 18 From a functional standpoint, peripheral NK-cells from patients with HCC showed lower IFNg production, but similar TNF-a and CD107a expression levels compared to controls.…”

Section: Discussionmentioning

confidence: 94%

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

et al. 2016

View full text Add to dashboard Cite

(controls) were phenotypically characterized. Unsupervised clustering based on the frequency of cells expressing different phenotypic NK-cell markers segregated HCC patients into different cohorts that were compared for outcome. NK-cell cytokine production and cytotoxicity were compared between cohorts with different overall survival (OS) and time to disease recurrence (TTR). By multivariate analysis, age, Child-Pugh class and NK-cell phenotypic clustering could independently identify patients with significantly different OS. NK-cells from patients with better outcome expressed higher levels of cytotoxic granules and CD3z and lower levels of natural cytotoxic receptors (NCRs) that were co-expressed with the inhibitory receptor NKG2A known to negatively regulate NCR function. Cytotoxic function and IFNg production were significantly lower in the cohort of patients with worse outcome compared to controls (p < 0.05). Our results show a role for NK-cells in the control of HCC progression and survival providing the basis for the development of immunotherapeutic strategies to potentiate NK-cell response.

show abstract

Section: Discussionmentioning

confidence: 94%

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Notably, age is known to interfere with NK cell functionality and phenotype. Elderly individuals show a reduction of the CD56 bright NK cell subset, whereas the CD56 dim NK cells show a reduction in the activating receptor expression (54). Then, the absence of significant association between occurrence of relapse and NK-DP-like AML transcription profile in the validation cohort could suggest that the wide heterogeneity of the disease and patient's age may counteract immunity's efficiency.…”

Section: Discussionmentioning

confidence: 96%

Defective NK Cells in Acute Myeloid Leukemia Patients at Diagnosis Are Associated with Blast Transcriptional Signatures of Immune Evasion

Khaznadar

Boissel

Agaugué

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a heterogeneous group of malignancies that may be sensitive to the NK cell antitumor response. However, NK cells are frequently defective in AML. In this study, we found in an exploratory cohort (n = 46) that NK cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK cell profile, including reduced expression of some activating NK receptors (e.g., DNAX accessory molecule-1, NKp46, and NKG2D) and decreased IFN-γ production, had a significantly higher risk of relapse (p = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g., IL15, IFNGR1, IFNGR2, and CXCR4), Ag processing (e.g., HLA-DRA, HLA-DRB1, and CD74) and adhesion molecule pathways (e.g., PVR and ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.

show abstract

“…Under normal conditions, exposure to exogenous IL-2 induces tenfold greater proliferation of CD56bright cells compared to CD56dim lymphocytes (Baume et al 1992). However, during aging there is a redistribution of NK cell subsets as shown by a decrease of CD56bright cells and an increase of CD56-CD16+ NK cells (Solana et al 2014, Krishnaraj 1997. In this way, the amount of IFN-γ secreted by NK cells from the elderly was only 25 percent of that released by the cells from younger samples (Krishnaraj 1997 (Chiu et al 2013, Elpek et al 2010).…”

Section: Natural Killersmentioning

confidence: 99%

“…Immunosenescence describing alterations including the decline of immune responses with age is comprised of inappropriate elevations, decreases, and dysregulated immune responses, leading to more severe consequences of bacterial and viral infections and reduced responses to vaccination (Montgomery and Shaw 2015). Elderly individuals usually present chronic low level inflammation, likely as the consequence of continued exposure to antigens combined with poor EdUArdo FUENTES, MANUEl FUENTES, MArCElo AlArCóN and IváN PAloMo immune function, increases in the production of pro-inflammatory cytokines by effector memory and senescent T cells and macrophages (Campos et al 2014). In addition, there may be disease impairment through a compromised adaptive immune response due to accelerated aging of the immune system in patients with an advanced clinical status (Moro-Garcia et al 2014).…”

mentioning

confidence: 99%

Immune System Dysfunction in the Elderly

Fuentes

Alarcón

et al. 2017

An. Acad. Bras. Ciênc.

184

147

View full text Add to dashboard Cite

Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic lowlevel inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

show abstract

Shaping of NK cell subsets by aging

Cited by 132 publications

References 55 publications

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

Defective NK Cells in Acute Myeloid Leukemia Patients at Diagnosis Are Associated with Blast Transcriptional Signatures of Immune Evasion

Immune System Dysfunction in the Elderly

Contact Info

Product

Resources

About