Inflammation, aging, and cancer vaccines

Abstract

Immunosenescence is characterized by a series of changes of immune pathways, including a chronic state of low-grade inflammation. Mounting evidence from experimental and clinical studies suggests that persistent inflammation increases the risk of cancer and the progression of the disease. Cancer vaccination, which came into view in the last years as the most intriguing means of activating an immune response capable of effectively hampering the progression of the preclinical stages of a tumour, has been shown to be less effective in older age than in young adults. Available evidence on the use of inhibitors of inflammation has indicated their potential enhancement of cancer vaccines, suggesting the possibility to improve the low effectiveness of cancer vaccines in old age employing pharmacological or natural compounds-based anti-inflammatory intervention. This review addresses the effects of age and inflammation on cancer development and progression, and speculates as to whether the modulation of inflammation may influence the response to cancer immunization.

Inflammation, chronic obstructive pulmonary disease and aging

“…Inflammation is a complex series of events, involving many cell types (macrophages, neutrophils, monocytes, dendritic, and mast cells), and their main molecular products, such as prostaglandins, cytokines, nuclear factor kB (NF-kB), chemokines, and angiogenic factors [6]. These factors, which are produced very early in the response to multiple stresses, are important in being involved in both host defense and disorder.…”

“…Epigenetics Changes in the histone acetylation patterns [56], general demethylation of repetitive elements, hypermethylation of promoters of specific genes [6] Increased histone acetylation of the pro-inflammatory genes [50], global hypomethylation of repetitive elements, gene-specific hypermethylation of tumor suppressor genes Epigenetic alterations are a common trait between COPD and aging Somatic mutations Recurrent DNA damage and inefficient repair commonly lead to an increased extent of heterogeneity in aging tissues [57] The somatic mutations of lung epithelial cells are thought to be directly involved in the development of the disorder [58] Both COPD and aging are characterized by an increase in somatic mutations…”

“…In particular, the well known downregulation of SIRT1 is associated with changes in the histone acetylation patterns [56]; histone methylation status is often altered [56]; the DNA methylation status shows changes similar to that observed in cancer tissues, with hypermethylation of specific promoters probably due to the progressive inefficacy of DNA methyltransferase 1 (DNMT1) and the subsequent overexpression of DNMT3b, and loss of global DNA methylation mainly due to a demethylation in repetitive elements [6]. In conclusion, the epigenomic alterations observed in cigarette smoke exposure experiments and/or COPD patients are partially coincident with that found in aging and cancer processes (Table 1).…”

Aging and cancer: can mTOR inhibitors kill two birds with one drug?

“…DR is well known to be anti-inflammatory [23,90,91]. For tumors, it is becoming more evident that an inflammatory microenvironment is of critical importance in cancer promotion and resistance to therapy, and that the anti-inflammatory, as well as the antitumor, effects of rapamycin (and rapalogs) are likely have beneficial effects in this compartment [92], including cancer stem cells [93]. Although there are no data to date, anti-inflammation in a prolongevity intervention involving chronic treatment with rapamycin could well be a major contributor to the extended lifespan observed in mice [56,57].…”

Biogerontology in Italy

“…In line with this studies are the works of Provinciali and coworkers (INRCA, Ancona) focusing the age-related immune dysfunction that leads to inflammaging but also to higher incidence of cancer (Provinciali 2009;Provinciali et al 2010), the group is looking for vaccine and immunization procedures for prevent tumors and to increase free-diseases life. Antonicelli and Coll.…”