Trichosanthin (TCS), extracted from the Chinese medicinal herb Trichosanthes kirilowi, has shown promise for the inhibition of
tumor growth. However, its immunomodulatory effect on
tumor-host interaction remains unknown. In this study, we focused on the effect of TCS on murine anti-
tumor immune response in the 3LL
Lewis lung carcinoma tumor model and explored the possible molecular pathways involved. In addition to inhibiting cell proliferation and inducing apoptosis in the 3LL
tumor, TCS retarded
tumor growth and prolonged mouse survival more significantly in C57BL/6 immunocompetent mice than in nude mice. This reflected the fact that the host immune system was involved in
tumor eradication. Using FACS analysis, we found that TCS increased the percentage of effector T cells, particularly
Interferon-gamma (IFN-γ) producing CD4(+) and CD8(+) T cells from
tumor-bearing mice. TCS also promoted the vigorous proliferation of
antigen-specific effector T cells, markedly increased Th1
cytokine secretion and elicited more memory T cells in
tumor-bearing mice, consequently enhancing the anti-
tumor response and inducing immune protection. Furthermore, we found that TCS upregulated the expression of
tumor suppressor in
lung cancer 1 (TSLC1) in 3LL
tumor cells and the expression of its
ligand,
class I-restricted T cell-associated molecule (
CRTAM), in effector T cells. Blocking TSLC1 expression with
small interfering RNA (
siRNA) significantly eliminated the effects of TCS on the proliferation and
cytokine secretion of effector T cells, suggesting that TCS enhances anti-
tumor immune response at least partially by boosting the interaction between TSLC1 and
CRTAM. Collectively, our data demonstrate that TCS not only affects
tumor cells directly, but also enhances anti-
tumor immunity via the interaction between TSLC1 and
CRTAM. These findings may lead to the development of a novel approach for
tumor regression.