Medicine and Health Sciences Commons^™

Modeling Of Cns Cancer With A Focus On The Immune Component, Daniel Zamler

Dissertations & Theses (Open Access)

The knowledge surrounding cancers of the central nervous system remains poorly developed, in particular with regard to the immune component. The works contained in this thesis look at craniopharyngioma, glioblastoma, and several forms of brain metastasis. While some attention is given to the tumor cells themselves, as well as the patient setting which these studies model, the immune component of disease progression and treatment plays a strong role in each and is the primary focus of the works contained.

Craniopharyngioma is a relatively rare tumor in adults. Although histologically benign, it can be locally aggressive and may require additional therapeutic …

The Enzymatic Function Of The Tir Domain: From Axon Degeneration To Innate Immunity, Kow Essuman

Arts & Sciences Electronic Theses and Dissertations

The Toll/Interleukin-1 Receptor (TIR) domain is an evolutionarily ancient protein domain conserved from bacteria to eukaryotes, and is an essential signaling component of innate immunity pathways. In animal innate immunity, TIR domains have primarily been described for their scaffolding function in assembling protein complexes in host defense. In plant immunity, TIR domains are key components of the intracellular Nucleotide Binding Leucine rich repeat (NLR) immune receptors that confer resistance to pathogens. These NLR receptors trigger cell death and an immune response upon activation, but their mechanism has remained elusive. In bacteria, TIR domain proteins have been suggested to function as …

T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde

Arts & Sciences Electronic Theses and Dissertations

Pancreatic cancer carries a dismal prognosis, and desperately needs viable therapeutic interventions beyond chemo-radiation. T cell-dependent immunotherapies have shown great promise in several tumor types, but have not been effective for the vast majority of pancreatic cancer patients. This is, in part, due to our limited understanding of how antigenicity of pancreatic lesions is recognized, and how adaptive immunity is overcome in this disease. We sought to study tumor-immune interactions and identify mechanisms for this immune-failure using several spontaneous and unperturbed mouse models of pancreatic adenocarcinoma. We found that early pancreatic lesions fail to elicit tumor-limiting CD4+ TH1 and CD8+ …

Enhancing The Immune Response Through Ikkbeta-Induced Activation Of Nf-Kappab, Emily Hopewell

USF Tampa Graduate Theses and Dissertations

Nuclear factor-κB (NF-κB) is one of the main regulators of inflammatory and immune responses. It is a family of transcription factors composed of five members: RelA, RelB, cRel, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). Homo- and hetero-dimers of family members are inhibited by inhibitor of &klappaB (IκB) family members and activated by IκB kinase (IKK) family members. The IKK family is comprised of IKKα, IKKΒ, and IKKγ. The focus of my dissertation delves into the role of NF-κB activation by IKKΒ in both an immunotherapy setting and its role in T cell mediated anti-tumor immune responses.

A central focus of immunotherapy …

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …