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 Another project in Dr. Blomberg’s laboratory involves clinical research with breast cancer patients. In collaboration with Michael H. Antoni, Ph.D., in the department of Psychiatry and Behavioral Sciences, Charles S. Carver, Ph.D., in the department of Psychology, Sharlene Weiss, R.N., Ph.D., in the department of Medicine, and members of the Cancer Prevention and Control Program at the University of Miami Sylvester Comprehensive Cancer Center, researchers are measuring the status of various immune parameters in patients in response to psychosocial intervention (e.g., group therapy, stress reduction). Preliminary experiments have shown that intervention patients have an improved immune response as seen by the ability of their T cells to proliferate in response to an antigen-specific receptor stimulus (anti-CD3). Current studies are measuring T, NK, and lymphokine-activated killer cells (LAK) cytotoxic function as well as potential TH1/TH2 differences by cytokine production resulting from T-cell stimulation. These studies are important to allow optimal immune response in cancer patients, which will better detect and destroy residual cancer and allow for better patient survival. SELECTED PUBLICATIONS 2002 Jin, Y, Fuller, L, Carreno, M, Esquenazi, V, Blomberg, BB , Wei, YT, Ciancio, G, Burke, GW 3rd, Tzakis, A, Ricordi, C, and Miller, J. Functional and phenotypic properties of peripheral T cells anergized by autologous CD3(+) depleted bone marrow cells. Human Immunology 63:567- 75, 2002. Burke, GW, Ciancio, C, Blomberg, BB , Rosen, A, Suzart, K, Roth, D, Kupin, W, Esquenazi, V, and Miller, J. Randomized trial of three different immunosuppressive regimens to prevent chronic renal allograft rejection. Transplantation Proceedings 34:1610-11, 2002. Ricordi, C, Tzakis, A, and Miller, J. Human bone marrow cells retrovirally transduced with the allogeneic class II gene, HLA-DR3beta, down regulate anti-allogeneic responses of autologous lymphoid cells. Human Immunology 63:S19, 2002. 2003 Mathew, JM, Blomberg, BB, Fuller, L, Burke, GW, Ciancio, G, Kenyon, N, Ricordi, C, Tzakis, AG, Esquenazi, V, and Miller, J. A novel microcell-mediated lympholytic assay for the evaluation of regulatory cells in human alloreactive CTL responses. Journal of Immunological Methods 272:67-80, 2003. Blomberg, BB , Hussini, S, Fainman, H, Mathew, JM, Hernandez, A, Carreno, M, Hnatyszyn, HJ, Garcia-Morales, R, Fuller, L, Rosen, A, Ricordi, C, Tzakis, A, Miller, J, and Esquenazi, V. Retroviral transduction of an allogeneic class II gene into human bone marrow down regulates allo-immune reactivity. Human Immunology 64:S128, 2003. Hernandez, A, Lindner, I, Blomberg, BB, Hussini, S, Burger, M, Mathew, JM, Carreno, M, Garcia-Morales, R, Fuller, L, Jin, Y, Rosen, A, Lee, KP, Miller, J, and Esquenazi, V. Suppression of allogeneic T-cell proliferation through blocking of NF-κB in the differentiation process of human dendritic cells. Human Immunology 64:S128, 2003. Mathew, JM, Alvarez, S, Vallone, T, Blomberg, BB, Joshua, M, and Esquenazi, V. A human- SCID-mouse-islet transplant model for the evaluation of the regulatory activity of donor bone marrow cells. Human Immunology 64:S7, 2003. Van Der Put, E, Sherwood, EM, Blomberg, BB, and Riley, RL. Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation, and apoptosis. Experimental Gerontology 38:1137-47, 2003. Blomberg, BB , Mathew, J, Fainman, H, Hussini, S, Carreno, M, Hnatyszyn, H, Garcia-Morales, R, Fuller, L, Vallone, T, Rosen, A, Esquenazi, V, UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 107
T U M O R I M M U N O L O G Y P R O G R A M Frasca, D, Nguyen, D, Van Der Put, E, Riley, RL, and Blomberg, BB. The age-related decrease in E47 DNA-binding does not depend on increased Id Inhibitory proteins in bone marrowderived B cell precursors. Frontiers in Bioscience 8:A110-16, 2003. Frasca D, Nguyen D, Riley RL, and Blomberg, BB. Effects of aging on proliferation and E47 transcription factor activity induced by different stimuli in murine splenic B cells. Mechanisms of Ageing and Development 124:361-69, 2003. Frasca, D, Nguyen, D, Riley, RL, and Blomberg, BB. Decreased E12 and/or E47 transcription factor activity in the bone marrow as well as in the spleen of aged mice. Journal of Immunology 170:719-26, 2003. Frasca, D, Van der Put, E, Riley, RL, and Blomberg, BB . Reduced Ig class switch in aged mice correlates with decreased E47 and activation-induced cytidine deaminase. Journal of Immunology 172:2155-62, 2003. HIGHLIGHTS/DISCOVERIES • 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). • Decreased transcription factor E2A is important for decreased Ig class switch and optimal humoral immunity. • Demonstrated improved immune response is shown by breast cancer patients after psychosocial intervention. ROLAND JURECIC, PH.D. Assistant Professor of Microbiology and Immunology DESCRIPTION OF RESEARCH The lifelong maintenance and regenerative capacity of the blood cell-forming (hematopoietic) system depend on self-renewal, lineage commitment, and differentiation of hematopoietic stem cells (HSC) and progenitors. HSC hold tremendous promise for the development of stem cell transplantation and cell and gene therapy protocols for treatment of various diseases. Research in Dr. Jurecic’s laboratory focuses on: 1) elucidation of genetic mechanisms that regulate self-renewal, lineage commitment, and differentiation of HSC, 2) identification and functional genetic analysis of novel genes that are involved in the leukemogenesis, and 3) developmental plasticity of HSC. Molecular Genetics of Stem Cell Self-Renewal and Maintenance Self-renewal of stem cells in diverse species and tissues suggests that evolutionarily conserved mechanisms regulate this common feature. Dr. Jurecic’s laboratory is studying the role of the evolutionarily conserved Pumilio family of RNAbinding proteins in self-renewal and maintenance of mammalian hematopoietic and neural stem cells. Gain of function experiments have shown that: 1) overexpression of mouse Pum genes leads to increased maintenance and suppression of multilineage differentiation of HSC and multipotent progenitors, and 2) Pum genes support maintenance and self-renewal of multipotent hematopoietic cells through regulation of the SCF/c-kit signaling pathway. Molecular Genetics of Hematopoietic Stem Cell Differentiation The developmental cascade from HSC to mature blood cells, defined by a series of commitment steps that gradually restrict the developmental potential of intermediate progenitor cells, is regu- 108 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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