Article

Aging, immunity, and cancer

Research Center on Aging, University of Sherbrooke, Quebec, Canada.
Discovery medicine (Impact Factor: 3.63). 06/2011; 11(61):537-50.
Source: PubMed

ABSTRACT

Age is the most important risk factor for tumorigenesis. More than 60% of new cancers and more than 70% of cancer deaths occur in elderly subjects >65 years. The immune system plays an important role in the battle of the host against cancer development. Deleterious alterations occur to the immune response with aging, termed immunosenescence. It is tempting to speculate that this waning immune response contributes to the higher incidence of cancer, but robust data on this important topic are few and far between. This review is devoted to discussing state of the art knowledge on the relationship between immunosenescence and cancer. Emerging understanding of the aging process at the molecular level is viewed from the perspective of this increased tumorigenesis. We also consider some of the most recent means to intervene in the modulation of immunosenescence to increase the ability of the immune system to fight against tumors. Future research will unravel new aspects of the immune response against tumors which will be modulable to decrease the burden of cancer in elderly individuals.

0 Followers
 · 
12 Reads
  • Source
    • "In addition to the physical stress of the fracture, aging may also be a major contributor since it is associated with a decline in immune functions in both innate and adaptive immune systems (Fulop et al., 2014;Larbi et al., 2011;Shaw et al., 2010;Solana et al., 2012). The phenomenon is collectively termed immunosenescence and is largely responsible for susceptibility to infections, decreased efficiency of vaccination and development of cancers (Dorshkind et al., 2009;Fulop et al., 2011Fulop et al., , 2013Panda et al., 2009). HF triggers a state of acute stress that bears similarities with severe burns, sepsis and stroke in which case there is progressive immunosuppression (Xiu and Jeschke, 2013) and increased susceptibility to infections (Edwards et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Healthy elderly individuals are particularly prone to catastrophic events at any moment of their lives. One stressful event for individuals aged 65 and older is a fall that results in a fracture of the hip (HF). HF causes a state of inflammation that may affect immune responses. In this connection, we have reported that HF induced alterations in neutrophil functions. Objective: To assess the impact of HF on classical (cM), intermediate (iM) and non-classical (ncM) monocyte subsets. Methods: Distribution, functions (chemotaxis, phagocytosis, superoxide production and cytokine production), phenotype and activation (NF-x03BA;B and PI3K) were evaluated in monocyte subsets before surgery and 6 weeks and 6 months after the event. Results: The distribution of cM and ncM was unchanged, but iM transiently increased before surgery. Sustained increases (iM response to CCL2 and CX3CL1) and decreases (cM and ncM response to CCL2) in chemotaxis were observed. Phagocytosis and superoxide production were impaired in cM but not in iM or ncM. Sustained expression of HLA-DR occurred in cM but not in iM and ncM. Sustained decreased expression of CD11b occurred only in ncM. Sustained decreases (cM and ncM) and increases (iM) in CCR2 expression were observed. An elevated expression of CX3CR1 was found only in iM. cM produced elevated quantities of TNFα. There was a transient oxidative burst of production before surgery in iM and a sustained decrease in ncM. IL-10 production was severely impaired in cM and decreased in iM prior to surgery. Sustained activation (cM), inhibition (ncM) and transient activation (iM) of NF-x03BA;B were observed. Activation of PI3K was severely impaired in cM and ncM but was sustained in iM. Conclusion: HF had more impact on cM and ncM functions than on iM. HF triggered a switch in cM functions from phagocytic to inflammatory elevated TNFα-producing cells. These changes may impact clinical outcomes of HF with respect to inflammation, opportunistic infections and physical recovery.
    Full-text · Article · Jan 2016 · Gerontology
  • Source
    • "Additionally, there is a reduction in host defense mechanisms including macrophage phagocytosis, ineffective chemotaxis, decreased bactericidal function of neutrophils, and altered capability of dendritic and natural killer cells [69]. " Inflamm-aging " often takes place and is associated with immunosuppression and low grade inflammation [69]. When secondary pulmonary infection occurs as a result of impaired host response, secondary inflammation develops [73]. "

    Full-text · Article · Jun 2015 · Mediators of Inflammation
  • Source
    • "It is well known that substantial changes in the immune system, in terms of function and phenotypic profile, occur with aging. It is clear that immune function declines with aging, as the elderly are more susceptible to infection and malignancy (Fulop et al., 2011), a phenomenon referred to as 'immunosenescence'. However, pro-inflammatory cytokines are reported to be elevated in the serum of the elderly (Krabbe et al., 2004), and some chronic inflammatory diseases are more frequent in the elderly when compared to the young (Lee et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aging has been reported to be associated with changes in immune function. Although frequent infection and the development of malignancy suggest the decline of immune function with aging, changes toward proinflammatory conditions also develop at the same time. Th17 cells are well known CD4(+) T cell subpopulation closely linked to chronic inflammation and autoimmunity. In this study, changes in the Th17 population were investigated to elucidate a possible mechanism for this response with aging. Splenocytes were isolated from 2-month-old (young) and 20-month-old (aged) mice. CD4(+)CD44(+) memory T cells and CD4(+)CD62L(+) naïve T cells were isolated and sorted using magnetic beads and flow cytometry. The frequency of IL-17-producing cells was measured using flow cytometry. The expression of IL-17 and Th17-related factors at the mRNA level was measured with RT-PCR. IL-17 and Il-1β expression in spleen tissues was additionally assessed using confocal microscopy. The proportion of IL-17-producing CD4(+) T cells was higher in the splenocytes among the old mice than those of the young mice. When splenocytes were cultured in Th17 polarizing conditions, the proportion of IL-17 producing CD4(+) T cells was higher in aged mice as well. This was consistently observed when naïve and memory cells were isolated and differentiated into Th17 respectively. In addition, the expression of retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt) and other Th17-related factors (AhR, CCR6, and CCL20) increased in the splenocytes of aged mice compared to the young mice. The expression of IL-1β, showing to promote Th17 differentiation, was higher in the aged mice. Likewise, CD4(+) T cell expression of IL-1R was higher in the aged mice, suggesting that the CD4(+) T cells of the aged mice are readily prepared to differentiate into Th17 cells in response to IL-1β. Confocal microscopy showed that cells positive for IL-1R or IL-1β were more frequent in the spleens of the aged mice. When an anti-IL-2 antibody was applied, the proportion of IL-17-producing cells increased more prominently in the young mice. We observed that IL-2 production and IL-2R expression were reduced in the aged mice, respectively, explaining the blunted response to the anti-IL-2 antibody treatment and the consequent minimal change in the Th17 population. We demonstrated that the proportion of Th17 cells increased in the aged mice both in naïve and memory cell populations. Elevation of IL-1R and IL-1β expression and the reduction in IL-2 and IL-2R expression in aged mice seemed to promote Th17 differentiation. Our results suggest that enhanced Th17 differentiation in aging may have a pathogenic role in the development of Th17-mediated autoimmune diseases.
    Preview · Article · Oct 2013 · Experimental gerontology
Show more