SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

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T U M O R I M M U N O L O G Y P R O G R A M T U M O R I M M U N O L O G Y P R O G R A M PROGRAM LEADER Diana M. Lopez, Ph.D. Professor of Microbiology and Immunology DESCRIPTION OF PROGRAM The Tumor Immunology Program presently consists of 15 faculty members from four different departments at the University of Miami School of Medicine. The program comprises multiple aspects of basic immunology and a substantial number of studies involving tumor systems and samples obtained from patients. The program investigates numerous characteristics of the immune system in relation to the development and treatment of cancer. GOALS OF PROGRAM 1) Elucidate the mechanisms underlying the activities of innate and adaptive immune cells. 2) Study various aspects of stem cell biology and bone marrow transplantation. 3) Analyze the role of T cells and B cells in the host defenses against tumors. 4) Study the mechanisms of tumor evasion of the immune system. 5) Devise novel immunotherapeutic protocols. PARTICIPANTS Adkins, Rebecca D., Ph.D. Microbiology and Immunology Blomberg, Bonnie B., Ph.D. Microbiology and Immunology Jurecic, Roland, Ph.D. Microbiology and Immunology Lee, Kelvin P., M.D. Microbiology and Immunology Levy, Robert B., Ph.D. Microbiology and Immunology Lichtenheld, Mathias G., M.D. Microbiology and Immunology Lopez, Diana M., Ph.D. Microbiology and Immunology Malek, Thomas R., Ph.D. Microbiology and Immunology Podack, Eckhard R., M.D., Ph.D. Microbiology and Immunology Riley, Richard L., Ph.D. Microbiology and Immunology Rosenblatt, Joseph D., M.D. Medicine Thomas, Giovanna R., M.D. Otolaryngology Tolba, Khaled, M.D. Medicine Torroella-Kouri, Marta, Ph.D. Microbiology and Immunology Vincek, Vladimir, M.D., Ph.D. Pathology HIGHLIGHTS • Recent findings reveal that the primary function of interleukin 2 (IL-2) is the generation of T regulatory cells and not T-cell proliferation and sensitization to cell death as previously thought. (T. Malek) • During in vitro priming, IL-2 promotes subsequent engraftment and successful adoptive tumor immunotherapy by persistent memory phenotypic CD8 + T cells. (T. Malek) • Heatshock fusion vaccines generate CD8 cytotoxic T lymphocytes (CTL) without CD4 help; progress towards novel and efficient tumor-specific vaccines is underway. (E. Podack) UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 103
T U M O R I M M U N O L O G Y P R O G R A M • CD30 is identified as a major negative regulator of cytotoxic lymphocytes; blocking CD30 signals in vivo may enhance anti-tumor immune responses. (E. Podack) • A phase I study testing a vaccine therapy protocol in advanced non-small cell lung carcinoma showed that the vaccine was safe and stimulated an immune response. Clinical benefit was seen in six patients. (E. Podack) • A role for perforin in lymphocyte homeostasis revealed that cytotoxicity by perforin is necessary to remove antigen-presenting cells and turn off T-cell activation. (E. Podack) • A unique peptide with immunoenhancing properties has been identified in a secreted form of human MUC1 and used in vaccination experiments. This peptide inhibits tumor development in the mammary cells transfected with the secreted MUC1 and also protects against a variety of other tumor types. (D. Lopez) • Thymuses of mammary tumor bearers are profoundly involuted, and this is not due to a decrease of the thymocytes proliferation. A minor increase of apoptosis was noted; however, the major cause of this phenomenon appears to be an arrest at an early stage of differentiation, possibly brought about by the direct or indirect effects of tumor derived factors. (D. Lopez and R. Adkins) • After allogeneic bone marrow transplant, the recipient can resist the engraftment of transplanted donor stem cells by using immune responses, which do not involve the two major pathways of T lymphocyte-mediated killing. This is a surprising finding and demonstrates that it is likely that for some transplants, different pathways in the recipient must be blocked to help the transplanted bone marrow engraft. (R. Levy) • Lymphocytes, which were added to donor stem cells before transplant to help or facilitate the engraftment by these stem cells after transplant, use different functions for the purposes of: 1) helping to “seed” the stem cells in the recipient, and 2) helping to maintain their permanent presence. (R. Levy) • Direct activation of protein kinase C (PKC) causes normal human hematopoietic CD34 + stem cells to differentiate into dendritic cells (DC). (K. Lee) • PKC activation causes many myeloid leukemias to differentiate into immunologically functional “leukemic” DC. These cells have potential utility as “cellular” anti-leukemia vaccines. (K. Lee) • Researchers identified two essential enhancers of the perforin gene and demonstrated that they are under the control of Stat5 molecules. This work sheds molecular light on fundamental principles of effector gene activation in cytotoxic lymphocytes. (M. Lichtenheld) • Compromised humoral immune response in aged individuals may be at least partially explained by antibody V H repertoire differences at the pre-B cell level (before antigen selection). (B. Blomberg) • Breast cancer patients show improved immune response after psychosocial intervention. (B. Blomberg) • The molecular deficits, which underlie dysfunctions in lymphocyte activity during old age, have yet to be well characterized. The finding that expression of a transcription factor (E47) and surrogate light chains, both of which are critical to B-lineage cell development, are decreased in aged B-cell precursors provides a molecular basis for understanding deficient lymphopoiesis in senescence. (R. Riley) 104 UM/Sylvester Comprehensive Cancer Center Scientific Report 2004
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G L O S S A R Y IFN—interferon IL
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SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

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