Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Immunobiology
First Advisor
Joshi, Nikhil
Abstract
Cancer's complexity is characterized by its genetic diversity, adaptability to environmental changes, and the extent of immunoediting that results from interactions with the immune system. T cells, tasked with eliminating mutated cells, have entered the cancer research spotlight due to their therapeutic potential to restore the natural host immune response against established tumors. However, their effectiveness is limited to a subset of cancers, and their inability to eradicate all tumors from the outset has perplexed researchers. Consequently, immunoediting, which encapsulates the interplay between T cells and developing tumor cells within their specific microenvironment, is a linchpin in determining cancer fate. Immunoediting is not a static phenomenon but a continuum that unfolds throughout cancer progression, varying with the tissue type in which it occurs. Delineating the tumor intrinsic and extrinsic factors that influence this process is therefore challenging, necessitating comprehensive models that capture the nuances at the tumor-immune interface. Such understanding is essential for fully harnessing the potential of T cells in enhancing treatment strategies. This dissertation employs various models to investigate the mechanisms of T cell control in early tumor progression and the impact of T cell presence on tumor growth and genetics. Chapter 1 reviews the current landscape of cancer immunology, detailing both historical and current models used in clinical and laboratory settings to understand the relationship between cancer and the immune system. Chapter 2 highlights the inception of the immunoediting theory and the incongruities it reveals through the study of sarcoma tumors initiated in genetically engineered mouse models (GEMMs). Chapter 3 uncovers a key T cell-mediated immunoediting process in sarcoma progression using newly modified GEMMs. Chapter 4 examines the effect of T cell presence on cell lines derived from emergent tumors and additional in vivo models to complement immunoediting studies. Lastly, in Chapter 5, I propose a framework that leverages diverse models to envisage the multifaceted dynamic between tumors and the immune system, offering insights into potential approaches for deepening our understanding of cancer progression.
Recommended Citation
Cheung, Julie F., "Diverse Models of Immunoediting: Exploring Tumor-T cell Interactions in Developing Cancers" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1470.
https://elischolar.library.yale.edu/gsas_dissertations/1470
