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Full-Text Articles in Medicine and Health Sciences
Defining The Cooperation Between Mhc-I And Mhc-Ii Neoantigen-Driven T Cell Responses To Develop Effective Personalized Immunotherapies, Charmelle Williams
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 Brafv600e Pten-/- Cdkn2a-/- YUMM1.7 (Y1.7) murine melanoma line with a paucity of endogenous neoantigens that is unresponsive to ICT, and …
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Arts & Sciences Electronic Theses and Dissertations
Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …
Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen
Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen
Arts & Sciences Electronic Theses and Dissertations
Classical dendritic cells (cDCs) are specialized antigen presenting cells that can be divided into distinct subsets based on the types of pathogens they respond to and the type of immune response they generate. The cDC1 subset is specialized in priming CD8 T cell responses through the process of cross-presentation. During cross-presentation, exogenous protein antigens are taken up by cDC1 and presented on MHCI molecules, allowing for the priming of CD8 T cells during conditions when DCs themselves are not directly infected. The ability to cross-present in vivo is unique to cDC1, and is essential for anti-viral responses and rejection of …
Identification Of A Novel Single Amino Acid Substitution (V666g) Of Jak1 From A Patient With Acute Lymphoblastic Leukemia Impairs Jak3 Mediated Il-2 Signaling, Alice Hernandez Grant
Identification Of A Novel Single Amino Acid Substitution (V666g) Of Jak1 From A Patient With Acute Lymphoblastic Leukemia Impairs Jak3 Mediated Il-2 Signaling, Alice Hernandez Grant
Open Access Theses & Dissertations
The Janus kinase (JAK) family, notably JAK1, JAK2 and JAK3 are recognized as oncogenic drivers in high risk Acute Lymphoblastic Leukemia (ALL). The bulk of activating JAK mutations are thought to occur within functional hot-spots across Janus Homology (JH) domains. The most frequently mutated regions is the JH2 pseudo-kinase, which provides a negative regulatory role to the adjacent catalytically active JH1 kinase domain. Despite the prevalence of JAK activating mutations and a need for new therapeutic inhibitors, there is a lack of understanding in the allosteric regulation of JAK kinases. Here we sought to identify mutations involved in driving ALL …
Generation, Identification And Characterization Of Novel Monoclonal Antibodies Against Ctla-4, Pd-1 And Btla For The Treatment Of Cancer, Rosabril Acuna
Generation, Identification And Characterization Of Novel Monoclonal Antibodies Against Ctla-4, Pd-1 And Btla For The Treatment Of Cancer, Rosabril Acuna
Open Access Theses & Dissertations
Members of the CD28 co-inhibitory receptor family, Cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4), Program death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) are type I transmembrane proteins expressed on a variety of immune cells. Co- inhibitory receptors deliver "off" signals that play an important role in down regulating immune cell activation. Manipulation of inhibitory signals have shown to be a powerful strategy in the treatment of autoimmune diseases, infectious diseases and various forms of cancer. In fact, the FDA (Food and Drug Administration) has approved the use of monoclonal antibodies against CTLA-4 (Ipilimumab) for the treatment of metastatic melanoma, against …
Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer
Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer
Arts & Sciences Electronic Theses and Dissertations
Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are …
Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie
Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie
Theses and Dissertations
Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …
Improving Hpv Vaccination Series Initiation Rates And Compliance Among Indigent Women In South Texas, Ages 19-26, Through Provider Recommendation And Additional Clinic Funding: A Quality Improvement Project, Lacey Cudd
Doctor of Nursing Practice
The purpose of this quality improvement project was to increase human papillomavirus vaccination series initiation rates among indigent women, ages 19-26, at a clinic in South Texas. The human papillomavirus is a sexually transmitted infection that has been associated with multiple types of cancers. Each year, approximately 6.2 million cases of the human papillomavirus infection are diagnosed; as many as 75% of all new infections occur among females 18-26 years of age. The human papillomavirus vaccination has a high efficacy in regards to cancer prevention, preventing as many as 76% of cancers with only one dose. The project included educating …
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Arts & Sciences Electronic Theses and Dissertations
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …
A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez
A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez
Open Access Theses & Dissertations
A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …
Altered Leptin Signaling On Dendritic Cells As A Potential Mechanism For Cancer Immunotherapy, Lorena Y. De Los Santos
Altered Leptin Signaling On Dendritic Cells As A Potential Mechanism For Cancer Immunotherapy, Lorena Y. De Los Santos
Open Access Theses & Dissertations
Leptin is a pleiotropic hormone synthesized primarily by white adipocytes and its receptors are expressed in a variety of tissues and cells such as in the hypothalamus and cells of the immune system. Multiple cell types can produce a considerable amount of leptin such as skeletal muscle, placenta, and osteoblasts to name a few and its synthesis has been shown to be regulated by sex hormones and a broad range of inflammatory mediators. Although leptin has been shown to directly affect immune response, we are interested in how leptin affects dendritic cell function and their ability to induce a proper …