Ecological impacts of cancer chemotherapy on hematopoietic and immune dynamics

Thesis

Chemotherapy remains a cornerstone of cancer treatment even as the advent of targeted therapies and immunotherapies have sought to offer greater efficacy with fewer side effects. In spite of its age and traditional usage, chemotherapy continues to offer new insights when reconsidered as an ecological disturbance to the patient’s ecosystem. Not only does this view help predict divergent recoveries from chemotherapy, but an ecological lens suggests new ways of how chemotherapy can be integrated with immune dynamics, modern drugs, and treatment protocols. This work seeks to use mathematical modeling frameworks to better understand the ecological impacts of cancer chemotherapy in the context of patient hematopoietic and immune systems. For bone marrow transplantation, repopulation trajectories are evaluated in the light of clonal hematopoiesis in donor populations and host marrow conditions. This work is then extended to look at how the deletion of an immunomodulatory drug target may lead to niche and ecological changes. In addition, a modeling framework is built to explore the role that lymphodepleting chemotherapy may have on stimulating the immune system to mount an anti-tumor T cell response. Finally, a reinforcement learning approach is used to devise optimal chemotherapy treatment strategies to maximize synergy with the immune system.

Authors: Park, DS

• DOI: 10.5287/ora-mnrke0mm8
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: chemotherapy; hematopoiesis; mathematical modeling
• Subjects: Biology; Cancer