Systems biology as a compass to understand cancer-immune interactions in humans

Roelands, J. (2022)

Doctoral Thesis

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 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.

• Immunogenomics
• Immune oncology
• Colon cancer
• Breast cancer
• Transcriptomics
• Cancer immunotherapy
• Immune escape

• All authors: Roelands, J.
• Supervisor: Tollenaar, R.A.E.M.
• Co-supervisor: Kuppen, P.J.K.; Hendrickx, W.R.L.
• Committee: Versteeg, H.H.; Bedognetti, D.; Gruijl, T.D. de; Medema, J.P.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-06-29
• ISBN (print): 9789464195163