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Elucidating The Roles Of Il-15 In The Tumor Microenvironment, Rosa Maria Santana Carrero

Dissertations & Theses (Open Access)

ELUCIDATING THE ROLES OF IL-15 IN THE TUMOR MICROENVIRONMENT

Rosa M. Santana Carrero, B.S.

Advisory Professors: Shao-Cong Sun, Ph.D. & Kimberly S. Schluns, Ph.D.

Interleukin-15 (IL-15) is a factor that promotes activation, proliferation, cytotoxicity, and survival of CD8 T cells and NK cells, and has been shown to have anti-tumor effects. Moreover, loss of IL-15 expression in human colorectal tumors correlates with increased risk of relapse, diminished survival, decreased density and proliferation of T cells. All together these findings suggest that IL-15 expressed locally in the tumor microenvironment (TME) is an important mediator of anti-tumor responses by tumor infiltrating lymphocytes …

Putative Roles Of Cd200 In The Leukemogenesis And Immune Evasion Of Leukemia Stem Cells, Shelley Herbrich

Dissertations & Theses (Open Access)

Acute myeloid leukemia (AML) stem cells (LSC) are capable of surviving current standard chemotherapy and are the likely source of deadly, relapsed disease. While stem cell transplant serves as proof-of-principle that AML LSCs can be eliminated by the immune system, the translation of existing immunotherapies to AML have been met with limited success. Consequently, understanding and exploiting the unique immune mechanisms of AML LSCs is critical. To identify novel immunotherapeutic targets, we sourced multiple large, publicly available datasets and identified CD200 as a potential stem-cell specific immune checkpoint in AML. We hypothesized that CD200 was a stem-cell specific mechanism of …

Vestigial-Like 1 Is A Shared Targetable Cancer-Placenta Antigen Expressed By Pancreatic And Basal-Like Breast Cancers, Sherille Denae Bradley

Dissertations & Theses (Open Access)

Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regression by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from tumors of PDAC patients. This led to the identification of a shared HLA-A*0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1), a novel putative TAA demonstrating overexpression in multiple tumor types and low or absent transcript expression in normal tissues with the exception of placenta. VGLL1-specific CTL isolated and expanded from the blood of a male PDAC patient …