SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

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