Question ID: WS-35
Submitted by: Eric Engels
February 4, 2011
Question: To what extent is the increase in cancer risk with aging due to immune senescence? Background: The incidence of many cancers rises with age, and the aging of the U.S. population will lead to an increasing cancer burden. To some extent, the increase in cancer incidence with age is attributable to the cumulative exposure to carcinogens, and the attendant accumulation of somatic mutations. Nonetheless, older adults also manifest progressive declines in host immune function with aging (i.e., immune senescence), which leads, for example, to decreased responses to vaccines and increased frequency of clinical infections. The contribution of immune senescence to the development of cancer in adults is unknown. Feasibility: Recent technological developments in characterizing the immune system allow investigators to address this question. It is possible to assess immune function in multiple dimensions, including quantification of recent thymic emigrant lymphocyte populations, lymphocyte immunophenotyping and gene expression profiling, and multiplex measurement of circulating cytokines. Cross-sectional and longitudinal assessments in older adults would allow characterization of changes in the immune system with aging. Concurrent measurement of these markers in cancer cases and controls, ideally in pre-diagnostic samples, would provide an assessment of the contribution of these immune changes to the development of cancer. Implications of success: Demonstration of an association between immune senescence and cancer risk would expand our understanding of the role of normal immunity in preventing cancer. Identification of an immune profile associated with elevated cancer risk may point towards novel prevention strategies or identify individuals who would most benefit from enhanced cancer screening.
Average Score: 3.0
 (1 evaluation)Provocativeness - 1.0
Novelty - 1.0
Public Health Significance - 5.0
Feasibility - 5.0
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Comments
Submitted By Yong Qian
Most cancers are developed under the normal immune system that remains intact at early stages of cancer development (pre-cancer cells, cancer cells, a small tumor and a major tumor). When a cancer reaches a late stage (with multiple tumors and metastasis), the immune system is suppressed. Thus, cancer invades and disable the immune system over time (by expressing or over-expressing self-recognition molecules at the early stage of cancer, and by destroying part or the whole process of antigen presentation at later stages of cancer).
Over time, people's immune responses are gaining due to vaccination and exposure to foreign material including virus, bacterial, fungal...through antigen presentation process and disease specific polyclonal antibodies. The sad thing it that the immune system cannot do antigen presentation process on people's own cells with genetic mutations since the self-recognition molecules prevent the immune system (including macrophages and dendritic cells) to do so. Novel strategies that force the immune system to make pre-cancer cell and cancer cell specific polyclonal antibodies may work for cancer prevention and treatment as well.
Submitted By Olivera Finn
This is an old idea but a very important one to finally properly evaluate.
