Date of Completion

Spring 5-1-2018

Thesis Advisor(s)

Pramod Srivastava; William Corwin

Honors Major

Molecular and Cell Biology

Disciplines

Cells | Hemic and Immune Systems | Medical Immunology | Therapeutics | Tissues

Abstract

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently either FDA approved or being used in clinical trials. Despite this progress, the true mechanism of action of these therapeutics is not fully understood. To begin to gain an idea of how the treatments worked and differed from one another, an immunological snapshot of the immune cell populations in mice under various conditions was analyzed and compared. Comparisons were done between mice of different strains (BALB/cJ and BL/6), mice of different ages (6-8 weeks and 8-12 months), naïve mice and tumor-bearing mice, mice with early tumors and mice with late tumors, as well as untreated and treated (anti-CTLA4 or anti-PD1) mice. Results from these sets of experiments showed that there are significant variations in regards to some immune cells between mice of different groups, which may have an impact on how the immune system functions and how effectively tumor regression occurs. These mice models serve as the basis for understanding how anti-CTLA4 and anti-PD1 therapeutics affect various immune cell populations and will help guide further research in this area.

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