The role of the adaptive immune response in controlling the growth and recurrence of human tumors has been controversial. We characterized the tumor-infiltrating immune cells in large cohorts of human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. Collectively, the immunological data (the type, density, and location of immune cells within the tumor samples) were found to be a better predictor of patient survival than the histopathological methods currently used to stage colorectal cancer. The results were validated in two additional patient populations. These data support the hypothesis that the adaptive immune response influences the behavior of human tumors. In situ analysis of tumor-infiltrating immune cells may therefore be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.

https://science.sciencemag.org/content/sci/313/5795/1960.full.pdf

Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome

Understanding how the immune system affects cancer development and progression has been one of the most challenging questions in immunology. Research over the past two decades has helped explain why the answer to this question has evaded us for so long. We now appreciate that the immune system plays a dual role in cancer: It can not only suppress tumor growth by destroying cancer cells or inhibiting their outgrowth but also promote tumor progression either by selecting for tumor cells that are more fit to survive in an immunocompetent host or by establishing conditions within the tumor microenvironment that facilitate tumor outgrowth. Here, we discuss a unifying conceptual framework called "cancer immunoediting," which integrates the immune system's dual host-protective and tumor-promoting roles.

http://science.sciencemag.org/content/sci/331/6024/1565.full.pdf

Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion

Infiltrating stromal and immune cells form the major fraction of normal cells in tumour tissue and not only perturb the tumour signal in molecular studies but also have an important role in cancer biology. Here we describe 'Estimation of STromal and Immune cells in MAlignant Tumours using Expression data' (ESTIMATE)--a method that uses gene expression signatures to infer the fraction of stromal and immune cells in tumour samples. ESTIMATE scores correlate with DNA copy number-based tumour purity across samples from 11 different tumour types, profiled on Agilent, Affymetrix platforms or based on RNA sequencing and available through The Cancer Genome Atlas. The prediction accuracy is further corroborated using 3,809 transcriptional profiles available elsewhere in the public domain. The ESTIMATE method allows consideration of tumour-associated normal cells in genomic and transcriptomic studies. An R-library is available on https://sourceforge.net/projects/estimateproject/.

/pdf/inferring-tumour-purity-and-stromal-and-immune-cell-3qvnp398w9.pdf

Inferring tumour purity and stromal and immune cell admixture from expression data

Tumours grow within an intricate network of epithelial cells, vascular and lymphatic vessels, cytokines and chemokines, and infiltrating immune cells. Different types of infiltrating immune cells have different effects on tumour progression, which can vary according to cancer type. In this Opinion article we discuss how the context-specific nature of infiltrating immune cells can affect the prognosis of patients.

The immune contexture in human tumours: impact on clinical outcome

Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.

/pdf/sex-differences-in-immune-responses-5lxzp3yqfg.pdf

Sex differences in immune responses

Though dietary factors are implicated in chronic disease risk, assessment of dietary intake has limitations, including problems with recall of complex food intake patterns over a long period of time. Diet and nutrient biomarkers may provide objective measures of dietary intake and nutritional status, as well as an integrated measure of intake, absorption and metabolism. Thus, the search for an unbiased biomarker of dietary intake and nutritional status is an important aspect of nutritional epidemiology. This chapter reviews types of biomarkers related to dietary intake and nutritional status, such as exposure biomarkers of diet and nutritional status, intermediate endpoints, and susceptibility. Novel biomarkers, such as biomarkers of physical fitness, oxidative DNA damage and tissue concentrations are also discussed.

Dietary intake and nutritional status.

Purpose
The mechanisms driving the physical activity–breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity–breast cancer association.

Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk

The oral micro biome is highly diverse and its composition is associated with oral disease and potentially diseases at other sites. Our objective is to evaluate DNA extraction methods potentially suitable for population-based investigations on the oral human microbiome and disease risk. Six commonly used microbial DNA extraction kits, employing either enzymatic methods or mechanical bead beating for cell lysis, were evaluated for the following aspects total DNA yield and quality and 16s rRNA DNA product and representation of microbial diversity. All analyses were carried out using a pooled and homogenized sample from one study subject. 16s rRNA gene sequence data were processed using the QIIME pipeline. One way ANOVA and Kruskal-Wallis tests were used to compare the different DNA extraction methods. We found that enzymatic extraction kits produced higher human genomic DNA, compared with mechanical extraction kits, however, phylogenic diversity in oral microbiome community structure from 16s rRNA gene sequence reads revealed no important differences between kit types. Enzymatic and mechanical bead beating kits provide alternative approaches for DNA extraction of oral microbiome DNA from oral wash samples. Greater total DNA yields are found in enzymatic approaches but microbial diversity can be similarly well characterized by either enzymatic or mechanical bead beating approaches. Original Research Article British Journal of Medicine & Medical Research, 4(10): 1980-1991, 2014 1981

Comparison of DNA extraction methods for human oral microbiome research.

Height and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

/pdf/height-and-risk-of-prostate-cancer-in-the-prostate-lung-1nccrx2660.pdf

Jiyoung Ahn

Papers

Dietary intake and nutritional status.

Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk

Comparison of DNA extraction methods for human oral microbiome research.

Height and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.

Antioxidant Supplements, Genetics and Chemotherapy Outcomes