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Articles 1 - 10 of 10
Full-Text Articles in Life Sciences
Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos
Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos
Dissertations & Theses (Open Access)
Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …
Enhancing Adoptive Cell Therapy By Augmenting Fitness And Anti-Tumor Function Of Tumor-Infiltrating Lymphocytes, Parin Shah
Dissertations & Theses (Open Access)
The success of immune checkpoint inhibitors (ICIs) has established the importance of cancer immunotherapy in solid cancers, where it has been adopted as one of the standards of care for advanced melanoma and lung cancer. It is currently being investigated to treat other solid cancers. However, a large fraction of patients do not respond to ICIs and relapse. ICI therapy offers an in vivo approach to activate tumor-specific T cells, albeit in some cases, this modality does not create a sufficiently robust anti-tumor response. Thus, ex vivo approaches employing manipulation of immune cells, such as Adoptive Cell Therapy (ACT) using …
Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra
Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra
Dissertations & Theses (Open Access)
Human Papillomavirus (HPV) induced cancers continue to affect millions of women worldwide, with the five year survival rate hovering just under 60% in some demographics. Therefore there is an unmet need to develop effective, yet, easily administered therapies to treat established HPV genital lesions. Even though immune checkpoint therapy (ICT) is a promising treatment option in some HPV+ cancers, the high cost and associated toxicities are still major concerns for their widespread application. HPV cancers are textbook candidates for therapeutic vaccination intervention because they’re driven by the expression of viral oncoproteins E6 and E7, which serve as ideal tumor specific …
Combination Of Oncolytic Adenoviruses, T-Cell Activation, And Blockade Of Ido Metabolic Circuitry For The Treatment Of Glioma, Teresa Nguyen
Combination Of Oncolytic Adenoviruses, T-Cell Activation, And Blockade Of Ido Metabolic Circuitry For The Treatment Of Glioma, Teresa Nguyen
Dissertations & Theses (Open Access)
Glioblastoma is the most common malignant primary brain tumor in adults; the current aggressive treatment results in a 5% five-year survival rate. More effective therapies should be developed. One promising alternative is oncolytic adenovirus, Delta-24-RGD, which elicits cancer cell lysis and immunogenic cell death. In fact, Delta-24-RGD produced complete responses in 20% of recurrent glioblastoma patients through immune mechanisms that activate anti-tumor cytotoxic properties of T-cells. This cytolytic effect can further be enhanced by adding immune agonists, namely OX40L, which engages the OX40 receptor to co-stimulate activated T cells for enhanced proliferation. Hence, we produced the next generation of Delta-24-RGD, …
Conserved Non-Pocket Interactions Drive The Diversity Of Peptide Presentation By Mhc Class I Molecules, Kyle Jackson
Conserved Non-Pocket Interactions Drive The Diversity Of Peptide Presentation By Mhc Class I Molecules, Kyle Jackson
Dissertations & Theses (Open Access)
Cytotoxic T-lymphocytes (CTL) can lyse infected or transformed cells through recognition of peptides presented on human leukocyte antigen (HLA) molecules. A thorough understanding of peptide-HLA interactions is needed for improvement of CTL-based immunotherapies. We observed that aspartic acid (D) and glutamic acid (E) at peptide position 4 are highly prevalent in HLA-I peptide ligands, and discovered that they interact with arginine (R) in position 65 and lysine (L) in position 66 of the α1 helix of the binding groove in HLA-A*0201 and HLA-A*2402. Since this interaction differed from well-characterized peptide-HLA anchor interactions mediated by peptide position 2 and the C-terminus, …
Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra
Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra
Dissertations & Theses (Open Access)
Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …
Hypoxia Acts As An Environmental Cue For The Human Tissue-Resident Memory T-Cell Differentiation Program, Farah Hasan
Hypoxia Acts As An Environmental Cue For The Human Tissue-Resident Memory T-Cell Differentiation Program, Farah Hasan
Dissertations & Theses (Open Access)
Tissue-resident memory T-cells (TRM) provide frontline defense against viral diseases and can contribute to anti-tumor immunity; however, aside from the necessity of TGF-β, little is known regarding cues for TRM differentiation. Oxygen tension is an environmental cue that distinguishes peripheral tissues from the circulation and here, we demonstrate that differentiation of human CD8+ T-cells under hypoxic conditions in the presence of TGF-β1 led to the development of a TRM phenotype, characterized by a greater than five-fold increase in CD69+CD103+ cells expressing human TRM hallmarks and enrichment for endogenous human TRM gene signatures, including increased …
Unraveling Host-Gut Microbiota Dialogue And Its Impact On Response To Immune Checkpoint Blockade, Alexandria Cogdill
Unraveling Host-Gut Microbiota Dialogue And Its Impact On Response To Immune Checkpoint Blockade, Alexandria Cogdill
Dissertations & Theses (Open Access)
Cancer is a disease with only one degree of separation, affecting one in two men and one in three women in their lifetimes; accounting for 1 of every 6 deaths. While cancer mortality rates continue to improve, incidence rates are expected to rise and shift through 2050 due to epidemiological and demographic transitions worldwide. As such, it is imperative to continue to investigate and improve our understanding of both disease etiology and hallmarks of response to treatment. Currently, conventional therapies include, but are not limited to, surgery, chemotherapy, and radiotherapy. However, within the past decade, major advances have been made …
The Role Of Pag1 In The Activated B-Cell Subtype Of Diffuse Large B-Cell Lymphoma, Jared Henderson
The Role Of Pag1 In The Activated B-Cell Subtype Of Diffuse Large B-Cell Lymphoma, Jared Henderson
Dissertations & Theses (Open Access)
Diffuse Large B Cell Lymphoma (DLBCL) is the most common aggressive hematologic malignancy in adults, but despite recent advances in treatment, many patients today still face poor outcomes. Of the two types of DLBCL, activated B-cell (ABC) and germinal center B-cell (GCB), patients diagnosed with the ABC subtype especially face a lack of effective treatment options. Unlike GCB-DLBCL, ABC-DLBCL is characterized by chronic antigen-driven signaling by the B-cell receptor (BCR), indicating an escape from immunologic tolerance mechanisms that normally regulate self-reactive B cells. While recent therapies have focused on inhibiting the kinases that propagate BCR signaling with mixed success, we …
Assessing The Outcomes Of Blocking Ccl2-Ccr2 Signaling Axis On Breast Cancer Brain Metastasis, Yutao Qi
Assessing The Outcomes Of Blocking Ccl2-Ccr2 Signaling Axis On Breast Cancer Brain Metastasis, Yutao Qi
Dissertations & Theses (Open Access)
Breast cancer brain metastases have remained one of the most intense challenges for precision cancer therapeutics, but current treatment options are limited and not curative. Recently, our lab reported that adoptive PTEN downregulation in metastatic breast tumor cells activates PI3K/NF-ƙB signaling and increases the secretion of the chemokine CCL2, which enhances the chemotaxis of CCR2+ myeloid cells, a major subpopulation of bone marrow-derived myeloid cells (BMDMs), from peripheral blood into the brain tumor microenvironment (TME), eventually promoting brain metastasis outgrowth by driving immune suppression. Here, in this project we have been aiming to develop effective therapies by immune-modulating the …