SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

More documents

Recommendations

Info

T U M O R I M M U N O L O G Y P R O G R A M REBECCA D. ADKINS, PH.D. Associate Professor of Microbiology and Immunology DESCRIPTION OF RESEARCH Cancer in infants and children differs markedly from that in adults. For example, there are some solid tumors that occur in children but never or rarely develop in adults, including neuroblastoma, Wilms tumor, rhabdomyosarcoma, osteosarcoma, hepatoblastoma, Ewing’s sarcoma, and retinoblastoma. Moreover, solid tumors as well as hematologic malignancies, such as acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), demonstrate distinct biological features and responses to treatment in children and adults. During the last half of the 20 th century, great strides were made in improving survival rates of many pediatric cancers. This was achieved largely by increasing the aggression of chemotherapy treatments. Because of the high intensity of current therapy, however, future improvements are unlikely to come from further increases in chemotherapy intensity. Moreover, chemotherapy is not ideal for use in children because of adverse side effects that can manifest in later life. In this light, it appears that the improved survival of pediatric cancer patients is awaiting the application of new therapeutic regimens. One relatively new and especially promising approach for treating cancers in adults is the application of immunotherapy. A good deal of attention is being paid to the possibility of enhancing endogenous anti-tumor responses. Because of the limitations with current therapies, the idea of enhancing the anti-tumor responses of children with cancer is very appealing. At the present time, however, all hands are tied because there simply is not enough known about the neonatal/juvenile immune system to devise the appropriate immunotherapeutic approaches. Using a mouse model system, Dr. Adkins has focused on studying the development of immune system function in neonatal life. Her laboratory has made many interesting and important observations that have significantly broadened the knowledge base of neonatal immunity. First, Dr. Adkins and her colleagues have shown that, unlike in adults, responses mediated by T lymphocytes differ in the newborn lymph nodes and spleen. Second, they have found that neonates show an abnormal persistence of anti-inflammatory T-cell responses following exposure to model vaccine antigens. Third, they have demonstrated definitively that the immature responses of neonatal T lymphocytes are due to inherent properties of this population of cells rather than immature signals in the neonatal environment. Lastly, they most recently discovered that the properties of neonatal T lymphocytes are at least partly due to an “imprinting” that occurs during embryonic life. Currently, Dr. Adkins and her colleagues are beginning to uncover the molecular regulation of the neonatal phenomenon. These studies will aim at identifying new tools that can be applied to enhancing neonatal immune responses. It is becoming increasingly apparent that murine newborns are immunologically quite similar to human fetuses and infants. On this basis, it reasonably can be argued that they stand to learn a great deal about what is potentially happening in humans by studying murine models. Thus, the long-term goal of these studies will be to utilize the information gained here to devise new strategies for the prevention and treatment of pediatric cancer. SELECTED PUBLICATIONS 2002 Muller-Sieburg, CE, Cho, RH, Thoman, M, Adkins, B, and Sieburg, HB. Deterministic regulation of hematopoietic stem cell self-renewal and differentiation. Blood 100:1302-9, 2002. Adkins, B, Bu, Y, and Guevara, P. Murine neonatal CD4+ lymph node cells are highly deficient in the development of antigen-specific Th1 function in adoptive adult hosts. Journal of Immunology 169:4998-5004, 2002. UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 105
T U M O R I M M U N O L O G Y P R O G R A M Lopez, DM, Charyulu, V, and Adkins, B. Influence of breast cancer on thymic function in mice. Journal of Mammary Gland Biology and Neoplasia 7:191-9, 2002. 2003 Petito, CK, Adkins, B, McCarthy, M, Roberts, B, and Khamis, I. CD4+ and CD8+ cells accumulate in the brains of acquired immunodeficiency syndrome patients with human immunodeficiency virus encephalitis. Journal of Neurovirology 9:36-44, 2003. Adkins, B, Williamson, T, Guevara, P, and Bu, Y. Murine neonatal lymphocytes show rapid early cell cycle entry and cell division. Journal of Immunology 170:4548-56, 2003. Auais, A, Adkins, B, Napchan, G, and Piedimonte, G. Immunomodulatory effects of sensory nerves during respiratory syncytial virus infection in rats. American Journal of Physiology—Lung Cellular and Molecular Physiology 285:L105-13, 2003. Adkins B, Bu Y, Vincek V, and Guevara P. The primary responses of murine neonatal lymph node CD4 + cells are Th2-skewed and are sufficient for the development of Th2-biased memory. Clinical and Developmental Immunology 10:43- 51, 2003. Adkins, B. Peripheral CD4 + lymphocytes derived from fetal versus adult thymic precursors differ phenotypically and functionally. Journal of Immunology 171:5157, 2003. BONNIE B. BLOMBERG, PH.D. Professor of Microbiology and Immunology DESCRIPTION OF RESEARCH Research in Dr. Blomberg’s laboratory focuses on two projects. One of those projects involves basic research on the molecular regulation of B lymphopoiesis in mice. Generation of B lymphocytes is important in cancer patients receiving bone marrow as well as in the normal production of the humoral (antibody) response. Aged humans and other mammals have a poorer immune response to pathogens. In collaboration with Richard L. Riley, Ph.D., in the department of Microbiology and Immunology, Dr. Blomberg has shown that aged mice, those greater than or equal to about 80 percent of their full life span, have a substantial decrease in the number of precursor B lymphocytes as well as the amount of the precursor B-cell receptor (preBCR) including the surrogate light chain (SLC)y5 and VpreB. Their data indicate that this affects the antibody V H repertoire at the pre-B cell level, i.e., before antigen selection. More recent data indicate that the transcription factor, E2A, is reduced in not only precursor B cells but also in mature B cells in peripheral lymphoid organs in aging, leading to defects in Ig class switch and humoral immunity. Current studies will reveal the molecular and cellular causes of these defects in the aged humoral immune response and attempt to reverse these defects. These studies are important for cancer for two reasons: 1) the depressed immune response seen in aged humans likely contributes to increased susceptibility to cancer, and 2) bone marrow transplantation given to many types of cancer patients requires generation of mature B lymphocytes from the precursors in the bone marrow. Knowledge about the cellular and molecular requirements for B lymphopoiesis in young and aged individuals should lead to improvements in the humoral immune system of cancer patients. 106 UM/Sylvester Comprehensive Cancer Center Scientific Report 2004
Page 1 and 2:
S C I E N T I F I C R E P O R T 2 0
Page 3 and 4:
I N T R O D U C T I O N A N D P R O
Page 5 and 6:
Page 7 and 8:
Page 9 and 10:
Page 11 and 12:
L E A D E R S H I P MULTIDISCIPLINA
Page 13 and 14:
L E A D E R S H I P EXTERNAL ADVISO
Page 15 and 16:
C A N C E R P R E V E N T I O N A N
Page 17 and 18:
Page 19 and 20:
Page 21 and 22:
Page 23 and 24:
Page 25 and 26:
Page 27 and 28:
Page 29 and 30:
Page 31 and 32:
Page 33 and 34:
Page 35 and 36:
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 45 and 46:
Page 47 and 48:
C L I N I C A L O N C O L O G Y R E
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68: C L I N I C A L O N C O L O G Y R E
Page 79 and 80: T U M O R C E L L B I O L O G Y P R
Page 117: T U M O R I M M U N O L O G Y P R O
Page 121 and 122: T U M O R I M M U N O L O G Y P R O
Page 143 and 144: V I R A L O N C O L O G Y P R O G R
Page 157 and 158: S H A R E D R E S O U R C E S 3) La
Page 159 and 160: S H A R E D R E S O U R C E S C E L
Page 161 and 162: S H A R E D R E S O U R C E S D N A
Page 163 and 164: S H A R E D R E S O U R C E S G E N
Page 165 and 166: S H A R E D R E S O U R C E S I N F
Page 167 and 168: S H A R E D R E S O U R C E S P O P
Page 169 and 170:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 171 and 172:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 173 and 174:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 175 and 176:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 177 and 178:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 179 and 180:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 181 and 182:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 183 and 184:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 185 and 186:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 187 and 188:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 189 and 190:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 191 and 192:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 193 and 194:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 195 and 196:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 197 and 198:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 199 and 200:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 201 and 202:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 203 and 204:
P U B L I C A T I O N S 2 0 0 2 - 2
Page 205 and 206:
G L O S S A R Y IFN—interferon IL
show all

SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

Create successful ePaper yourself

Delete template?

Save as template?