Autoimmunity in the elderly: Implications for cancer

Malaguarnera, Michele; Cristaldi, Erika; Romano, Giulia; Malaguarnera, Mariano

doi:10.4103/0973-1482.106527

Cited by 22 publications

(6 citation statements)

References 64 publications

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“…While we do not know the exact cause of this association, plausible explanations can be hypothesized. First, physiologically, aging is associated with immunosenescence, which may escalate tumor spread in elderly patients [16]. Second, patient compliance may affect the timing of seeking care for treatment.…”

Section: Discussionmentioning

confidence: 99%

Changes in the Clinicopathological Demographics of Vulvar Cancer in Japan: Increasing Oldest-Old, Stage Shifting, and Decreasing Cohort-Level Survival †

Nishio

Matsuo

Shibata

et al. 2019

JCM

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Background: To examine trends in the clinicopathological characteristics of vulvar cancer in Japan. Methods: This is a nationwide retrospective study examining consecutive women with vulvar cancer between 2001 and 2010 in Japan (n = 1061). Temporal trends in demographics, tumor characteristics, and survival were assessed by cohort-level analysis. The National Cancer Institute’s Surveillance, Epidemiology, and End Result Program was used for external validation (n = 10,154). Results: The number of oldest-old women aged ≥80 years significantly increased (from 18.0% in 2001 to 30.6% in 2010; 70.5% relative increase) in the study period. A stage shift was observed, with stage I disease decreasing from 43.0% to 34.0% (21.0% relative decrease), and tumors with distant metastases increasing from 23.2% to 35.6% (53.3% relative increase, p < 0.05). The number of women who underwent surgical treatment decreased from 84.0% to 69.7% (17.0% relative decrease), whereas utilization of radiotherapy increased from 34.4% to 43.2% (25.7% relative increase) over time (p < 0.05). In the cohort-level analysis, the five-year survival rates significantly decreased from 2001 to 2010 (p < 0.05), specifically, 66.9% to 51.0% for progression-free survival (23.7% relative decrease), 79.5% to 67.9% for cause-specific survival (14.6% relative decrease), and 74.9% to 62.3% for overall survival (16.9% relative decrease). In the patient-level analysis, oldest-old women were less likely to undergo surgical treatment and were independently associated with decreased survival (p < 0.05). In the US cohort, the number of oldest-old women (25.2% to 27.8%) and the five-year cause-specific survival rate (81.8% to 79.9%) remained unchanged during the study period (p > 0.05). Conclusion: Demographics and outcomes of vulvar cancer in Japan significantly changed during the study period. An increasing oldest-old population and a stage shift to more metastatic disease resulted in a cohort-level decrease in survival rates.

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Section: Discussionmentioning

confidence: 99%

Changes in the Clinicopathological Demographics of Vulvar Cancer in Japan: Increasing Oldest-Old, Stage Shifting, and Decreasing Cohort-Level Survival †

Nishio

Matsuo

Shibata

et al. 2019

JCM

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“…A putative protective mechanism may be associated with an enhanced function of the immune system in early life [25] with a role of ApoE as an immunomodulator [52]. At old ages immunosenescence may be a factor favoring neoplasia [53]. Then, if ApoE4 boosts the immune system in early life, this may naturally lead to prematurely exhausting this system later in life which may affect cancer survivorship for carriers of this allele (and, thus, implying antagonistic pleiotropy).…”

Section: Discussionmentioning

confidence: 99%

Age, Gender, and Cancer but Not Neurodegenerative and Cardiovascular Diseases Strongly Modulate Systemic Effect of the Apolipoprotein E4 Allele on Lifespan

et al. 2014

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Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham Heart Study (FHS) original and offspring cohorts and the Long Life Family Study (LLFS) to investigate gender-specific effects of the ApoE4 allele on human survival in a wide range of ages from midlife to extreme old ages, and the sensitivity of these effects to cardiovascular disease (CVD), cancer, and neurodegenerative disorders (ND). The analyses show that women's lifespan is more sensitive to the e4 allele than men's in all these populations. A highly significant adverse effect of the e4 allele is limited to women with moderate lifespan of about 70 to 95 years in two FHS cohorts and the LLFS with relative risk of death RR = 1.48 (p = 3.6×10−6) in the FHS cohorts. Major human diseases including CVD, ND, and cancer, whose risks can be sensitive to the e4 allele, do not mediate the association of this allele with lifespan in large FHS samples. Non-skin cancer non-additively increases mortality of the FHS women with moderate lifespans increasing the risks of death of the e4 carriers with cancer two-fold compared to the non-e4 carriers, i.e., RR = 2.07 (p = 5.0×10−7). The results suggest a pivotal role of non-sex-specific cancer as a nonlinear modulator of survival in this sample that increases the risk of death of the ApoE4 carriers by 150% (p = 5.3×10−8) compared to the non-carriers. This risk explains the 4.2 year shorter life expectancy of the e4 carriers compared to the non-carriers in this sample. The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can non-additively interfere with cancer-related mechanisms.

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“…Increasing age results in what has been described as immunosenescense, 26,27 with reduced lymphocyte numbers, as well as an enrichment of myeloid cells in peripheral blood and lymphoid tissue, an increased number of memory T cells (both CD4+ and CD8+), especially Th17 cells. 28,29 In addition, there are changes in the innate immune system, such as reduced phagocytosis and an increased production of proinflammatory cytokines including interleukin-6 and interleukin-8 in aged macrophages, with the potential that this will reduce their ability to clear extracellular debris and apoptotic cells in vivo and as well induce a shift in macrophage subtypes from the “M2” to the “M1” subtype. 30 It has been suggested that immunosenescence may in part be driven by a persistent cytomegalovirus infection, which although not causing overt clinical disease, is continually activating the immune system.…”

Section: An Aging Retina Vs An Aging Immune Systemmentioning

confidence: 99%

Immune Responses in Age-Related Macular Degeneration and a Possible Long-term Therapeutic Strategy for Prevention

Nussenblatt¹,

Lee²,

Chew³

et al. 2014

American Journal of Ophthalmology

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Purpose To describe the immune alterations associated with, age related macular degeneration (AMD). Based on these findings, to offer an approach to possibly prevent the expression of late disease. Design Perspective Methods Review of the existing literature dealing with epidemiology, models, and immunologic findings in patients. Results Significant genetic associations have been identified and reported, but environmentally induced (including epigenetic) changes are also an important consideration. Immune alterations include a strong interleukin-17 family signature as well as marked expression of these molecules in the eye. Oxidative stress as well as other homeostatic altering mechanisms occurs throughout life. With this immune dysregulation there is a rationale for considering immunotherapy. Indeed immunotherapy has been shown to affect the late stages of AMD. Conclusion Immune dysregulation appears to be an underlying alteration in AMD as in other diseases thought to be degenerative and due to aging. Parainflammation and immunosensescence may importantly contribute to the development of disease. The role of complement factor H still needs to be better defined but in light of its association with ocular inflammatory conditions such as sarcoidosis, it does not appear to be unique to AMD but rather may be a marker for retinal pigment epithelium function. With the strong interleukin-17 family signature and the need to treat early on in the disease process, oral tolerance may be considered to prevent disease progression.

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Autoimmunity in the elderly: Implications for cancer

Cited by 22 publications

References 64 publications

Changes in the Clinicopathological Demographics of Vulvar Cancer in Japan: Increasing Oldest-Old, Stage Shifting, and Decreasing Cohort-Level Survival †

Changes in the Clinicopathological Demographics of Vulvar Cancer in Japan: Increasing Oldest-Old, Stage Shifting, and Decreasing Cohort-Level Survival †

Age, Gender, and Cancer but Not Neurodegenerative and Cardiovascular Diseases Strongly Modulate Systemic Effect of the Apolipoprotein E4 Allele on Lifespan

Immune Responses in Age-Related Macular Degeneration and a Possible Long-term Therapeutic Strategy for Prevention

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