Perspectives on cancer immuno‐epidemiology

Abstract

Estimating human cancer risk based on host-environment interaction is one task of epidemiology, and it has provided indispensable knowledge for prevention of cancer. The recent development of gene-engineered mice has also provided solid evidence about the relationship between cancer development and immunity. The aim of this review is to discuss the possible contribution of epidemiology to understanding the role of immunity in host defense against cancer, and also to assess the involvement of inflammation in the occurrence of selected cancers. Here we look at the concepts of cancer immunosurveillance and infectioninflammation-cancer, and include a brief introduction to recent studies in humans and experimental animal models. It has been postulated for many years that the immune system has the ability to recognize and eliminate nascent transformed cells in the body (so-called cancer immunosurveillance hypothesis), and this idea has recently obtained strong support from animal experiments. In humans, follow-up studies among immunosuppressed transplant recipients revealed a remarkably increased risk of not only selected malignancies, but also cancers with no known viral etiology. On the other hand, a prospective cohort study among the general population revealed that individuals with low natural cytotoxic activity of peripheral blood lymphocytes had an increased risk of cancer development. More studies are warranted to allow the construction of a model for the interaction between host immunity, aging, and the environment. The host immune system is also involved in inflammatory responses to pathogen infection: insufficient immune function of the host, or repeated infection, may result in persistent inflammation, where growth/ survival factors continuously act on initiated cells. The combined use of biomarkers will be necessary to define low-grade persistent inflammation in future cohort studies; and, in addition to these phenotype marker-based cohort studies, one plausible future direction will be a genomic approach that can be undertaken within cohort studies, looking at the genetic background underlying individual variations in phenotype markers. pidemiological studies investigate the association between cancer development and various environmental or/and host factors in human populations, providing models to estimate cancer risk as a quantitative function of these factors (e.g., exposure levels, physiological status) among individuals. We anticipate that epidemiological studies will work well under the following conditions: 1) the intensity of factors varies among individuals (being expected to produce substantial differences in cancer risk); 2) adequate measurements are available to evaluate the intensity or grade of factors (in the case of biomarkers); 3) a relevant basic biological concept or laboratory evidence-supported working hypothesis describing the relation between cancer and these factors is available; and 4) the association between cancer and these factors, if it exists, will contribute to cancer preve...

Risk Factors for Pituitary Tumors: A Case-control Study

“…Past epidemiologic studies have consistently reported reduced risks of glioma in relation to atopic disease (30), and although causality has not been established, the association might be due to raised tumor immunosurveillance in subjects with allergy (31). Such an effect might also be present for pituitary tumors, although our findings could potentially also be explained by other factors, including selection bias among controls, bias in recall of allergy, and reverse causality.…”

Identification of the NKG2D Haplotypes Associated with Natural Cytotoxic Activity of Peripheral Blood Lymphocytes and Cancer Immunosurveillance

“…Using an 11-year follow-up of this cohort study-where the cytotoxic activity (measured at baseline by the isotope release method using K567 as target cells) was categorized into high, medium, and low levels by tertiles-we previously reported that individuals with high or medium levels of natural cytotoxic activity of peripheral blood lymphocytes had a decreased risk of cancer development compared with those with low cytotoxic activity (6). This was the first evidence of the vital role played by natural immunologic defense in the occurrence of common cancers among the general population (who do not have obvious defects in their immune systems), indicating the possible feasibility of cancer immunoprevention and the usefulness of natural cytotoxic activity as a surrogate biomarker for this prevention (7).…”

“…This finding could lead us to a new field, cancer immunoprevention, which would aim to enhance the ability of the immune system to recognize and Research. eliminate nascent transformed cells in the body (7). The innate immune system, in its initial response to a pathogen, may also be involved in determining how long and how strongly inflammation will continue after pathogen infection, in some cases leading to a sequential process of infection to inflammation to cancer (25,26).…”

Targeted therapy for cancer stem cells: the patched pathway and ABC transporters

“…Rapid regression of a tumor following cytotoxic therapy could lead to a disruption of the tumor niche and subsequent death of the cancer stem cells. For many tumors, there is also an important role played by immune surveillance (Nakachi et al, 2004), and reducing the size of the tumor may allow the immune system to more efficiently eliminate the remaining cells.…”