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
• CD30 is identified as a major negative regulator
of cytotoxic lymphocytes; blocking CD30 signals
in vivo may enhance anti-tumor immune
responses. (E. Podack)
• A phase I study testing a vaccine therapy protocol
in advanced non-small cell lung carcinoma
showed that the vaccine was safe and stimulated
an immune response. Clinical benefit was seen
in six patients. (E. Podack)
• A role for perforin in lymphocyte homeostasis
revealed that cytotoxicity by perforin is necessary
to remove antigen-presenting cells and turn
off T-cell activation. (E. Podack)
• A unique peptide with immunoenhancing
properties has been identified in a secreted form
of human MUC1 and used in vaccination experiments.
This peptide inhibits tumor development
in the mammary cells transfected with the
secreted MUC1 and also protects against a variety
of other tumor types. (D. Lopez)
• Thymuses of mammary tumor bearers are profoundly
involuted, and this is not due to a decrease
of the thymocytes proliferation. A minor
increase of apoptosis was noted; however, the
major cause of this phenomenon appears to be
an arrest at an early stage of differentiation, possibly
brought about by the direct or indirect
effects of tumor derived factors. (D. Lopez and
R. Adkins)
• After allogeneic bone marrow transplant, the
recipient can resist the engraftment of transplanted
donor stem cells by using immune responses,
which do not involve the two major
pathways of T lymphocyte-mediated killing.
This is a surprising finding and demonstrates
that it is likely that for some transplants, different
pathways in the recipient must be blocked
to help the transplanted bone marrow engraft.
(R. Levy)
• Lymphocytes, which were added to donor stem
cells before transplant to help or facilitate the
engraftment by these stem cells after transplant,
use different functions for the purposes of: 1)
helping to “seed” the stem cells in the recipient,
and 2) helping to maintain their permanent
presence. (R. Levy)
• Direct activation of protein kinase C (PKC)
causes normal human hematopoietic CD34 +
stem cells to differentiate into dendritic cells
(DC). (K. Lee)
• PKC activation causes many myeloid leukemias
to differentiate into immunologically functional
“leukemic” DC. These cells have potential utility
as “cellular” anti-leukemia vaccines. (K. Lee)
• Researchers identified two essential enhancers
of the perforin gene and demonstrated that they
are under the control of Stat5 molecules. This
work sheds molecular light on fundamental
principles of effector gene activation in cytotoxic
lymphocytes. (M. Lichtenheld)
• Compromised humoral immune response in
aged individuals may be at least partially explained
by antibody V H
repertoire differences at
the pre-B cell level (before antigen selection).
(B. Blomberg)
• Breast cancer patients show improved immune
response after psychosocial intervention. (B.
Blomberg)
• The molecular deficits, which underlie dysfunctions
in lymphocyte activity during old age,
have yet to be well characterized. The finding
that expression of a transcription factor (E47)
and surrogate light chains, both of which are
critical to B-lineage cell development, are decreased
in aged B-cell precursors provides a molecular
basis for understanding deficient
lymphopoiesis in senescence. (R. Riley)
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2004