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
Dix, RD, Podack, ER, and Cousins, SW. Murine
cytomegalovirus retinitis during retrovirus-induced
immunodeficiency (MAIDS) in mice:
interleukin-2 immunotherapy correlates with increased
intraocular levels of perforin mRNA. Antiviral
Research 59:111-19, 2003.
Raez, L, Cassileth, PA, Schlesselman, JJ,
Padmanabhan, S, Fisher, EZ, Baldie, PA,
Sridhar, K, and Podack, ER. Induction of CD8
T-cell-Ifn-γ response and positive clinical outcome
after immunization with gene-modified
allogeneic tumor cells in advanced non-small-cell
lung carcinoma. Cancer Gene Therapy 10:850-
58, 2003.
HIGHLIGHTS/DISCOVERIES
• Completed successful lung tumor vaccine trial.
• Discovered that MΦ-perforin, a new member
of the perforin family, promises interesting discoveries.
• Discovered that death receptor 3 does not kill,
but produces, IL-13, which is immunosuppressive
and mediates asthma.
• Realized potential of heat shock proteins to
enter the clinical field of immunotherapy.
RICHARD L. RILEY, PH.D.
Professor of Microbiology and Immunology
DESCRIPTION OF RESEARCH
Altered B Cell Development in Senescence
Senescent mice show diminished B lymphopoiesis
when compared to young mice and typically
exhibit decreased numbers of pre-B cells and
newly formed B cells within the bone marrow.
Researchers in Dr. Riley’s laboratory have focused
upon elucidating the mechanisms responsible for
the altered B lymphopoiesis in old age and the
ramifications for antibody repertoire and humoral
immunity. In particular, he and his colleagues
have found that B lymphopoiesis in old
age is partially interrupted at the pro-B to pre-B
cell transition, a developmental step that requires
both function of the pre-B cell receptor complex
and responses to the growth and survival cytokine
interleukin-7 (IL-7). Expression of a critical component
of the pre-B cell receptor, the surrogate
light chain, is reduced in aged mice, and IL-7
responsiveness is diminished. This predisposes the
B-cell precursors in aged mice to apoptotic cell
death. These functions, and others important to
B-cell development, are governed, in part, via the
transcriptional regulator E2A. E2A expression
also is compromised in old age; this appears to
involve enhanced degradation of E2A proteins.
As a consequence of the B-cell developmental
deficits in old age, the repertoire of antibody
specificities is skewed and the capacity to develop
effective immune responses is hindered.
SELECTED PUBLICATIONS
2002
Riley, RL, Knowles, J, and King, AM. Levels of
E2A protein expression in B cell precursors are
stage-dependent and inhibited by stem cell factor
(c-kit ligand). Experimental Hematology
30:1412-18, 2002.
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.
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.
Sherwood, EM, Xu, W, and Riley, RL. B cell precursors
in senescent mice exhibit decreased recruitment
into proliferative compartments and
altered expression of Bcl-2 family members.
Mechanisms of Ageing and Development
124:147-53, 2003.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2004