A growing body of scientific literature documents a putative role of commensal and pathogenic bacteria in the initiation and progression of cancers. One such bacterium is nontyphoidal Salmonella ... Show moreA growing body of scientific literature documents a putative role of commensal and pathogenic bacteria in the initiation and progression of cancers. One such bacterium is nontyphoidal Salmonella (NTS), which has been associated with colon cancer in a few studies. Yet, a lot is still unknown about the magnitude and underlying mechanisms, including the necessary conditions or ‘prerequisites’, of the potential colon carcinogenesis promoting effects of Salmonella. In this thesis, we performed several complementary analyses based on both experimental and epidemiological study designs. Significant excess risk of NTS infection was observed among several occupational groups including those involving contact with live animals or animal manure and animal-derived food sale. The risk of colon cancer was not elevated in these groups. Also, no clear association between NTS and colon cancer was found in a Danish cohort. Two-fold infection of mouse embryonic fibroblasts (MEFs) with a low dose of NTS was more successful than a single high-dose infection (i.e. more and larger colonies). Substantial variation between NTS isolates was found in their capacity to infect MEFs and to induce cellular transformation, with a tendency towards higher transformation efficiency in isolates originating from people who were diagnosed with colon cancer later in life. Show less
This thesis describes the steps necessary for the addition of the tumor-stroma ratio (TSR) into clinical practice as high-risk factor besides the TNM classification. The route from laboratory... Show moreThis thesis describes the steps necessary for the addition of the tumor-stroma ratio (TSR) into clinical practice as high-risk factor besides the TNM classification. The route from laboratory biomarker development to clinical implementation is followed. During this process, the relationship of the TSR to other available biomarkers for prognostic information for breast and colon cancer patients is investigated. Additionally, the prognostic value of the TSR in lung cancer is studied. Show less
Major achievements in the field of immune oncology have demonstrated the ability of the immune system to induce a response against cancer. The prognostic impact of pre-existing immunity in several... Show moreMajor achievements in the field of immune oncology have demonstrated the ability of the immune system to induce a response against cancer. The prognostic impact of pre-existing immunity in several cancer types, including breast and colon cancer, demonstrates the influence of the immune system on disease progression. At the same time, immunotherapeutic approaches that aim to enhance antitumor immune reactions have significantly improved the clinical outcome for a subset of patients. However, a large proportion of patients (60-80%) do not respond to immunotherapeutic treatments. To extend the benefit of immunotherapeutic strategies to a larger number of patients, it is imperative to understand the mechanisms associated with immune responsiveness. Different variables have been described to influence the development of antitumor immunity in cancer patients, including the tumor’s genetic program, the genetic makeup of the patients, and environmental factors such as the microbiome. These factors likely act in concert to modulate antitumor immune responses. This thesis aimed to dissect the molecular determinants of cancer immune responsiveness in human tumors. A systems biology approach was used to define underlying factors that shape the tumor microenvironment and reveal potential mechanisms of immune escape. Show less
