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Increasing T Cell Immunity to Metastatic Osteosarcoma via Modulation of Inhibitory T Cell Receptors


Abstract Osteosarcoma is the most common bone cancer in children and adolescents. Patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T-lymphocytes (CTL) limit the development of metastatic osteosarcoma. I have investigated the role of Programmed Death Receptor-1 (PD-1) in limiting the efficacy of immune mediated control of metastatic osteosarcoma. I show that human metastatic, but not primary, osteosarcoma tumors express the ligand for PD-1 (PD-L1) and that tumor infiltrating CTL express PD-1, suggesting this pathway may limit CTL control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mi... (more)
Created Date 2015
Contributor Lussier, Danielle Marie (Author) / Blattman, Joseph N. (Advisor) / Anderson, Karen (Committee member) / Goldstein, Elliott (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Subject Immunology / Molecular biology / Cellular biology / CTLA-4 / Inhibitory Receptors / Metastatic Osteosarcoma / PD-1 / PD-L1 / T cell exhaustion
Type Doctoral Dissertation
Extent 218 pages
Language English
Copyright
Reuse Permissions All Rights Reserved
Note Doctoral Dissertation Molecular and Cellular Biology 2015
Collaborating Institutions Graduate College / ASU Library
Additional Formats MODS / OAI Dublin Core / RIS


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Description Dissertation/Thesis