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*
Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy;
Departments of Cell Biology and Molecular Biology, Human Genome Sciences, Inc., Rockville, MD 20850;
Department of Oncology and Neurosciences, University of Chieti, Chieti, Italy; and
§
Institute for Cancer Research, University of Bologna, Bologna, Italy
The human ß chemokine known as LEC (also called NCC-4, HCC-4, or
LMC) displays chemotactic activity for monocytes and dendritic cells.
The possibility that its local presence increases tumor immunogenicity
is addressed in this paper. TSA parental cells (TSA-pc) are poorly
immunogenic adenocarcinoma cells that grow progressively, kill both
nu/nu and syngeneic BALB/c mice, and give rise to lung
metastases. TSA cells engineered to release LEC (TSA-LEC) are still
able to grow in nu/nu mice, but are promptly rejected
and display a marginal metastatic phenotype in BALB/c mice. Rejection
is associated with a marked T lymphocyte and granulocyte infiltration,
along with extensive macrophage and dendritic cell recruitment. NK
cells and CD4+ T lymphocytes are uninfluential in TSA-LEC
cell rejection, whereas both CD8+ lymphocytes and
polymorphonuclear leukocytes play a major role. An antitumor immune
memory is established very quickly after rejection, since 6 days later
75% of BALB/c mice were already resistant to a TSA-pc challenge.
Spleen cells from rejecting mice display specific cytotoxic activity
against TSA-pc and secrete IFN-
and IL-2 when restimulated by
TSA-pc. The ability of LEC to markedly improve recognition of poorly
immunogenic cells by promoting APC-T cell cross-talk suggests that it
could be an effective component of antitumor
vaccines.
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