Rebecca 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 or acute myeloid leukemia, demonstrate distinct biological features and responses to treatment in children and adults. During the last half of the 20th century, great strides were made in improving survival rates of many pediatric cancers. This was achieved largely by increasing the aggression of chemotherapy treatments. However, because of the high intensity of current therapy, 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 which 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 especially promising approach for treating cancers in adults is the application of immunotherapy - i.e., applying selective treatment regimens to enhance endogenous anti-tumor responses. Because of the limitations with current therapies, the idea of enhancing the anti-tumor responses of children with cancer is also very appealing. However, at the present time, our 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 group 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 adults, responses mediated by T lymphocytes differ in the newborn lymph nodes and spleen. Second, the group has found that neonates show an abnormal persistence of anti-inflammatory T cell responses following exposure to model vaccine antigens. Third, the group has demonstrated that inherent properties of neonatal T lymphocytes contribute substantially to their immature responses. Fourth, Dr. Adkins' laboratory has made the striking observation that neonatal mice mount mature, highly protective responses in the intestinal immune system. This contrasts with systemic responses which are often diminished or qualitatively different from responses elicited in adults. Lastly, the group recently discovered that the properties of neonatal T lymphocytes are at least partly due to an epigenetic "imprinting" that occurs during embryonic life. These ongoing studies are particularly relevant to malignancies in early life since it has become increasingly clear that epigenetics influence the development and progression of cancer.
Currently, Dr. Adkins and her colleagues are investigating the cellular and molecular mechanisms that regulate the properties of the neonatal immune system. These studies will be aimed at identifying new tools that can be applied to enhancing neonatal immune responses. Importantly, since murine newborns are immunologically quite similar to human fetuses and infants, we 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.
- Found that, unlike in adults, responses mediated by T lymphocytes differ in newborn lymph nodes and spleen.
- Found that neonates show an abnormal persistence of anti-inflammatory T-cell responses following exposure to model vaccine antigens.
- Demonstrated immature responses of neonatal T lymphocytes are due to inherent properties of this population of cells.
- Observed that neonatal mice mount mature, highly protective responses in the intestinal immune system.
- Discovered properties of neonatal T lymphocytes are at least partly due to an epigenetic “imprinting” that occurs during embryonic life.
Selected Cancer-Related Publications
- Echeverry A, Saijo S, Schesser K, Adkins B. Yersinia enterocolitica Promotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates. Infect Immun 78:3595-608, 2010 Read more »
- Opiela SJ, Koru-Sengul T, Adkins B. Murine neonatal recent thymic emigrants are phenotypically and functionally distinct from adult recent thymic emigrants. Blood 113:5635-43, 2009. Read more »
- Zaghouani H, Hoeman CM, Adkins B. Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells. Trends Immunol 30:585-591, 2009 Read more »
Collaborating in the Multidisciplinary Research Program(s):