Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 65 for “"Immune Checkpoint Blockade"”.
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Immune Checkpoint Blockade Induces Gut Microbiota Translocation That Augments Extraintestinal Anti-Tumor Immunity
Gut microbiota are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anti-cancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut …
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Unraveling Host-Gut Microbiota Dialogue and Its Impact On Response to Immune Checkpoint Blockade
… medicine that leverages the power of the human immune system to fight disease. In this way, it affords robust treatment choices for patients thought to have intractable disease. One specific type of immunotherapy shown to have a significant clinical benefit for cancer patients is monoclonal …
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Potentiation of The Immune Checkpoint Blockade Response By Metabolic Modulation Is Predictable Using Molecular Imaging
… tumor microenvironment (TME) for antitumor immune cells, protecting the tumor from immune cell-mediated control and immunotherapy. Two of these environmental factors, acidosis and hypoxia, are commonly found in solid cancers. In my thesis, I posited that modulation of tumor acidosis and …
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Studying the B and plasma cell responses to the immune checkpoint blockade treatment of cancer
Immune checkpoint blockade (ICB) therapies targeting PD-1 and CTLA-4 have revolutionised cancer treatment. However, their efficacy is not completely understood, especially regarding their effects on anti-tumour B and plasma cell responses, which are now regarded as important components of the …
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Defining the relationship between the gut microbiome and response to combination immune checkpoint blockade across cancer types
Immune checkpoint inhibitors (ICIs) targeting the proteins Programmed cell Death protein 1 (PD-1) and Cytotoxic T Lymphocyte associated protein 4 (CTLA-4) have revolutionised the treatment of many cancers, and can be used in combination for synergistic anti-tumour effect. Nevertheless, response to …
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Orthotopic liver metastasis mouse models of mismatch repair-proficient colorectal cancer recapitulate clinical inefficacy of immune checkpoint blockade
… in patients with colorectal cancer (CRC). Immune checkpoint blockade (ICB) therapy has significantly improved overall survival in several cancer types including melanoma and non-small cell lung cancer. However, patients with mismatch repair-proficient (pMMR) metastatic CRC do not respond to …
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T Cell Exhaustion in Glioblastoma
… treatment strategies such as immunotherapy. Immune checkpoint blockade is a type of immunotherapy which seeks to perpetuate T cell activity by blocking inhibitory immune checkpoints. This strategy has gained FDA approval in several solid tumors, yet has failed in GBM. Severe T cell …
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Development of Implantable Optical Fibers for Immunotherapeutics Delivery and Tumor Impedance Measurement
Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient-response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply …
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Integrative Cancer Immunogenomic Analysis of Serial Melanoma Biopsies Reveals Correlates of Response and Resistance to Sequential Ctla-4 and Pd-1 Blockade Treatment
… melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this …
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Understanding The Role of Arglu1 In Interferon Signaling Activation In Breast Cancer
… deadly disease. Novel cancer immunotherapy with immune checkpoint blockade (ICB) could induce long-lasting responses and improve survival in hard-to-treat malignancies. Regrettably, only a fraction of breast cancer patients respond to this highly promising strategy. To improving ICB therapy in …
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DISSECTING RESISTANCE TO IMMUNOTHERAPY IN MSS COLORECTAL CANCER
… (MSI) often display favorable responses to immune checkpoint inhibitor (ICI) therapies, in contrast to mismatch repair proficient and microsatellite stable (MSS) tumors. While the high mutational burden and elevated neoantigen levels in MSI CRCs are recognized as key determinants of ICI …
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Enhancing Anti-Cancer Immunotherapy by Disruption of the non-Receptor Tyrosine Kinase Fes
… are based on the principle that a patient’s own immune system can be engaged to fight their disease. While effective activation of the immune system is crucial for the success of cancer immunotherapies, native checkpoint mechanisms exist to limit immune activation and maintain homeostasis. In the …
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The Immunosuppressive Function of VEGF Signaling in the Tumor Microenvironment
… the efficacy of COX-2 inhibition and VEGF blockade in preclinical models of pancreatic cancer and identity it as a strategy to overcome therapy-induced resistance in pancreatic cancer. Combination therapy reverses anti-VEGF-induced epithelial-mesenchymal transition, collagen deposition and …
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Investigation of endogenous and adoptively transferred T cell function in a genetic mouse model of lung adenocarcinoma
The clinical success of immune checkpoint blockade, including in patients with lung cancer, has clearly demonstrated that the body's immune system is capable of tumor cytotoxicity if modulated appropriately. Unfortunately, only a minority of patients with solid tumors respond to checkpoint …
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Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation To Promote Immune Suppression
… immunity and demonstrated striking synergy with immune checkpoint blockade. Further, an RA responsive gene signature in human monocytes correlated with an immunosuppressive TME in multiple human tumors. RA has been long considered as an anti-cancer agent, but our work demonstrates its tumorigenic …
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The role of uterine natural killer cell-inhibition in pregnancy
… and transcriptome, as well as fetal growth. Immune checkpoint blockade of NKG2A during pregnancy in wild-type mice did not affect fetal growth, suggesting acute ablation of this pathway does not interfere with pregnancy outcome. In addition, generation of a humanised mouse model to test the …
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AXL Targeting Restores PD-1 Blockade Sensitivity of STK11/LKB1 Mutant NSCLC Through Expansion of TCF1+ CD8 T Cells
… are associated with poor patient responses to immune checkpoint blockade (ICB) for unknown reasons. We found that introduction of a Stk11/Lkb1 (L) mutation into murine lung adenocarcinomas driven by mutant Kras and Trp53 (KP) resulted in an ICB refractory syngeneic KPL tumor. Mechanistically, …
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Smac Mimetic and Combination Immunotherapy for the Treatment of Urothelial Cell Carcinoma
… carcinoma (MB49) resistant to prominent immune-stimulating therapies BCG mycobacterium and PD-1/PD-L1 checkpoint blockade. I found treatment with a monovalent SM, LCL161, generated T lymphocyte-dependent cures of MB49, retaining potent anti-tumour immune memory and significantly improving …
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Coordinated Blockade of TGF-β and PD-L1 Promotes Anti-Tumor Immunity in Ovarian Cancer Models
… diagnosis and high recurrence rates. Current immune checkpoint blockade (ICB) therapies show limited efficacy in HGSC, with no approved immunotherapy options for patients. This is due to an immunosuppressive tumor immune microenvironment (TIME) that limits the efficacy of ICB. Resistance to …
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Therapeutic Strategies to Target LILRB Receptors on Myeloid Cells for Cancer Immunotherapy
The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells which inhibit anti-tumor immunity are recognized as one of the major obstacles in cancer treatment. LILRB3 and LILRB4, immune …
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