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
SELECTED PUBLICATIONS
2002
Tolba, KA, Bowers, WJ, Eling, DJ, Casey, AE,
Kipps, TJ, Federoff, HJ, and Rosenblatt, JD.
Herpes simplex virus (HSV)-amplicon-mediated
delivery of LIGHT enhances the antigen-presenting
capacity of chronic lymphocytic leukemia.
Molecular Therapy 6:455-63, 2002.
Tolba, KA, Bowers, WJ, Muller, J, Housekneckt,
V, Giuliano, RE, Federoff, HJ, and Rosenblatt,
JD. Herpes simplex virus (HSV) amplicon-mediated
codelivery of secondary lymphoid tissue
chemokine and CD40L results in augmented antitumor
activity. Cancer Research 62:6545-51,
2002.
Rosenblatt, JD, Shin, SU, Nechustan, H, Yi,
KH, and Tolba, K. Potential role of chemokines
in immune therapy of cancer. Israel Medical
Association Journal 4:1054-59, 2002.
MARTA TORROELLA-KOURI, PH.D.
Assistant Professor of Microbiology
and Immunology
DESCRIPTION OF RESEARCH
When tumor cells initially emerge in a
healthy organism, they are recognized by
the immune system. This recognition leads to an
incipient defense reaction and elimination of the
initial tumor cell population. For unknown reasons,
however, some tumors progress, infiltrate,
and eventually metastasize and kill the host. Before
this occurs, a progressive decline in the immune
response of the host is observed. Today,
researchers know that the tumor is directly responsible
for this immunodepression observed in
tumor-bearing organisms.
The study of the interplay between a tumor
and its host, in terms of the mechanisms displayed
by the tumor that eventually control and
diminish the otherwise healthy immune response
of the host organism, is the center of Dr.
Torroella-Kouri’s research. She is particularly interested
in the role of the innate immune response
in cancer. Researchers in her laboratory
work with a mouse mammary tumor model in
which they observe a profound decrease in the
immune response of tumor-bearing animals. Specifically,
and among many other events, a deregulation
in the production of cytokines, important
mediators in cell-to-cell communication, is observed.
One of them, the critical cytokine
interleukin-12 (IL-12), produced by macrophages
and dendritic cells (DC), is seriously decreased in
the diseased animals. IL-12 has not only been
shown to play a central role in the communication
between the innate and induced immune
responses, but also recently has been the center of
much clinical interest due to its recognized antitumor
properties.
The laboratory has shown that several mammary
tumor-derived factors appear to be responsible
for the decreased production of IL-12 in the
tumor host. Their present research focuses particularly
in elucidating the mechanisms through
which the tumor-derived phospholipid phosphatidylserine,
as well as the cytokine IL-6, overproduced
in tumor-bearing animals, are able to
impair IL-12 expression in tumor animals. The
understanding of the molecular mechanisms governing
the expression of the critical cytokine IL-
12 in the context of the interaction between a
tumor and the immune system is essential in efforts
aimed at designing therapeutic strategies to
treat malignant disorders. Given its many roles,
direct applications of IL-12 or modulation of IL-
12 levels will remain an important aspect of research
for the treatment of cancer. The
laboratory’s tumor system, which like in the human
situation presents a severe impairment of IL-
12 production, is an excellent model in which to
design future translational research.
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 125