Medicine and Health Sciences Commons^™

Defining The Cooperation Between Mhc-I And Mhc-Ii Neoantigen-Driven T Cell Responses To Develop Effective Personalized Immunotherapies, Charmelle Williams

Dissertations & Theses (Open Access)

Immune checkpoint therapy (ICT) (e.g. anti-CTLA-4 (α-CTLA-4), anti-PD-1 (α-PD-1)) enables durable T cell-dependent anti-tumor immunity in certain cancer patients. Since a subset of patients respond to ICT, this work aims at developing a more in-depth understanding of T-cell responses to MHC class I (MHC-I) and MHC class II (MHC-II) tumor antigens that are derived from aberrant expression of non-mutant antigens or driver and passenger somatic alterations that can function as tumor neoantigens. We used a poorly immunogenic Braf^v600e Pten^-/- Cdkn2a^-/- YUMM1.7 (Y1.7) murine melanoma line with a paucity of endogenous neoantigens that is unresponsive to ICT, and …

The Role Of Ifitm3 In The Immune Response Of Brca-Deficient High Grade Serous Ovarian Carcinoma, Han Cun

Dissertations & Theses (Open Access)

Background: Prior studies showed that BRCA-deficient high grade serous ovarian carcinoma (HGSOC) had increased tumor infiltrating lymphocytes (TILs) compared to BRCA-wildtype (WT). To better understand the underlying immune mechanism in these tumors, a preliminary transcriptome analysis was performed on a set of microdissected HGSOC tumor specimens with BRCA1-mutation, BRCA2-mutation, or WT. This demonstrated an upregulation of IFITM3, an essential gene in modulating immune function. Based on these findings, we hypothesized that BRCA-deficient HGSOC have increased DNA damage leading to upregulation of IFITM3 and subsequent increase in antigen presentation and T-cell activation.

Methods: Following IRB approval, preliminary transcriptome analysis was performed …

Equipment To Address Infrastructure And Human Resource Challenges For Radiotherapy In Low-Resource Settings, Rachel Mccarroll

Dissertations & Theses (Open Access)

Millions of people in low- and middle- income countries (LMICs) are without access to radiation therapy and as rate of population growth in these regions increase and lifestyle factors which are indicative of cancer increase; the cancer burden will only rise. There are a multitude of reasons for lack of access but two themes among them are the lack of access to affordable and reliable teletherapy units and insufficient properly trained staff to deliver high quality care. The purpose of this work was to investigate to two proposed efforts to improve access to radiotherapy in low-resource areas; an upright radiotherapy …

Managing Variant Discrepancy In Hereditary Cancer: Clinical Practice, Barriers, And Desired Resources, Ellen Zirkelbach

Dissertations & Theses (Open Access)

Variants are changes in the DNA whose phenotypic effects may or may not be definitively understood. Because variant interpretation is a complex process, sources sometimes disagree on the classification of a variant, which is called a variant discrepancy. This study aimed to determine the practice of genetic counselors regarding variant discrepancies and to identify the barriers to counseling a variant discrepancy in hereditary cancer genetic testing. This investigation was unique because it was the first to address variant discrepancies from a clinical point of view. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. …

Cancer Diagnosis During Pregnancy: Evaluating The Challenges Faced By Oncologists, Shannon Kaye Mulligan

Dissertations & Theses (Open Access)

Cancer during pregnancy is occurring more often than in the past, and it is estimated that cancer is diagnosed in approximately 1/1000 pregnancies. A consensus exists that management of these patients should prioritize survival of the mother and minimize teratogenic effects to the fetus, and utilize a multidisciplinary approach, involving medical oncology, surgical oncology, radiation oncology, radiology, and a maternal fetal medicine specialist. In spite of this consensus, there is not a standardized approach for treating cancer in women diagnosed during pregnancy. Due to the relative infrequency of this situation in the oncologic setting, the aims of this study were …

A Randomized Trial Of Bilevel Positive Airway Pressure Device And High Flow Oxygen For Persistent Dyspnea In, David Hui

Dissertations & Theses (Open Access)

Background: Dyspnea is a common and distressing symptom among patients with advanced cancer. The role of bilevel positive airway pressure (BIPAP) and Vapotherm in the relief of dyspnea have not been well defined. We aimed to determine and to compare the efficacy of BIPAP and VapoTherm for cancer related dyspnea.

Methods: In this randomized, open-label, crossover study, we randomly assigned advanced cancer patients with persistent dyspnea >=3/10 to either Vapotherm for 2 hours followed by BiPAP for 2 hours, or BiPAP followed by Vaptherm. A variable washout period was instituted between interventions. The primary end point was change in numeric …