Remodeling of the immunoinflammatory network system in elderly cancer patients: Implications of inflamm-aging and tumor-specific hyperinflammation

Abstract

Although it is generally accepted that aging increases postoperative morbidity and mortality rates, the underlying mechanism remains unknown. The present review evaluates the clinical implications of remodeling the immunoinflammatory status with reference to inflammaging and tumor-specific hyperinflammation. We conducted a Medline/PubMed search for articles investigating factors related to aging and their effects on postoperative outcomes. Inflamm-aging results in both decreased immunity to exogenous antigens and increased auto-reactivity, whereby the beneficial effects of inflammation devoted to the neutralization of harmful agents early in life become detrimental late in life. Cancer also represents an immunologic challenge, which upregulates the systemic immune response. Thus, tumor-related hyperinflammation and inflamm-aging synergistically lead to the systemic priming of inflammatory mediators preoperatively; then, surgical stress acts as the second hit, increasing the risk of an exaggerated postoperative inflammatory response. Age-related molecular events may place elderly patients at greater risk of postoperative complications which could result in death. For regulating uncontrolled hyperinflammation, the clinical advantages of perioperative immunonutrition or steroids have been advocated; however, double-blind, randomized, controlled trials of pharmacologic modulation therapy are needed.

Aging, cancer, and cancer vaccines

“…There is also evidence of an increased concentration of IL-6, TNF-α, and various acute-phase proteins, suggesting that aging is associated with low-grade inflammatory phenotype [10-13,28,29], despite the absence of any particular disease [30,31]. …”

“…If the exposure of T-cells is prolonged, the antigenic stimulation could become chronic, potentially contributing to a pro-inflammatory phenotype [35] and determining persistent T-cell clonal expansion. This scenario is commonly observed in the case of cancer (tumor-associated antigens), autoimmunity, and during the aging process (prevalently due to chronic stimulation by CMV antigens) [28,36]. The accumulated clones, whose number (absolute number and number of expanded cell lines) represents an important component to determine the immune risk profile of an individual [28,29], physically occupy a part of the "immunological space" [3] and probably alternate/suppress the immune responses of other specific clones [2].…”

“…This scenario is commonly observed in the case of cancer (tumor-associated antigens), autoimmunity, and during the aging process (prevalently due to chronic stimulation by CMV antigens) [28,36]. The accumulated clones, whose number (absolute number and number of expanded cell lines) represents an important component to determine the immune risk profile of an individual [28,29], physically occupy a part of the "immunological space" [3] and probably alternate/suppress the immune responses of other specific clones [2]. Moreover, CMV-reactive clones are dysfunctional: they present the characteristics of anergic cells and a marked apoptosis resistance [32,33].…”

Perioperative Immunonutrition in Major Abdominal Surgery

“…In contrast, little is known about nutritional interventions after diagnosis of cancer (Valdes-Ramos and Benitez-Arciniega 2007). Cancer patients carry usually two negative prognostic factors, a substantial tumor load and a compromised immune system (Miki et al 2008;Valdes-Ramos and Benitez-Arciniega 2007;Zajac et al 2003). Altered T cell function with Th2 dominance represents the most consistent and dramatic change in the elderly patient.…”

Effect of Ageing on Systemic Inflammatory Response in Acute Pancreatitis

“…Elderly patients usually develop an exaggerated inflammatory response after surgery and this has been attributed to the proinflammatory status of older people [22]. However, when pro-inflammatory cytokine levels are analyzed, contradictory reports are found in the literature: (a) increased and delayed levels of interleukin (IL)-6 have been observed in elderly patients after surgery [23]; (b) monocyte activation and hypercytokinemia have been observed in elderly patients after surgical intervention [24]; (c) significantly higher levels of tumour necrosis factor (TNF)-alpha, IL-6, and IL-1-beta are produced by mitogen-stimulated peripheral mononuclear cells from the elderly when compared to young subjects [19].…”