Trypanosoma cruzi, the protozoan
parasite that causes
Chagas' disease, has anti-
cancer effects mediated, at least in part, by
parasite-derived products which inhibit
growth of
tumor cells. We investigated whether
immunity to T. cruzi
antigens could induce anti-
tumor activity, using two
rat models which reproduce
human carcinogenesis colon cancer induced by
1,2-dimethylhydrazine (
DMH), and
mammary cancer induced by N-nitroso-N-methylurea (NMU). We found that
vaccination with T. cruzi epimastigote lysates strongly inhibits
tumor development in both
animal models.
Rats immunized with T. cruzi
antigens induce activation of both CD4+ and CD8+
T cells and splenocytes from these
animals showed higher cytotoxic responses against
tumors as compared to
rats receiving adjuvant alone.
Tumor-associated
immune responses included increasing number of CD11b/c+ His48- MHC II+
cells corresponding to
macrophages and/or
dendritic cells, which exhibited augmented
NADPH-
oxidase activity. We also found that T. cruzi lysate
vaccination developed
antibodies specific for
colon and mammary
rat cancer cells, which were capable of
mediating antibody-dependent cellular cytotoxicity (
ADCC)
in vitro. Anti-T. cruzi
antibodies cross-reacted with
human colon and
breast cancer cell lines and recognized 41/60 (68%)
colon cancer and 38/63 (60%)
breast cancer samples in a series of 123
human tumors. Our results suggest that T. cruzi
antigens can evoke an integrated anti-
tumor response involving both the cellular and humoral components of the
immune response and provide novel insights into the
understanding of the intricate relationship between
parasite infection and
tumor growth(AU)