Investigate the immune suppressive mechanisms in
Bladder tumor
Date: 2010/5/14 10:00 a.m.
Room: R132
Speaker: Yun-che Ho
Advisor: Shu-fen Wu
Abstract
Transitional cell carcinoma (TCC) is tumor of the urinary system which is the most common
type of bladder cancer. TCC arises from the transitional epithelium a tissue between flat squamous
cell and tall columnar cell. According to our previous data, the percentage of NK cells in PBMC from
TCC patients are significantly lower than age match control especially at the superficial stage,
however, the percentage of CD4+CD25+ T cells are much higher in TCC patients. Base on the above
data, we want to investigate whether the NK cytotoxic function and regulatory T cell function are
modulated by transitional cell carcinoma. Last session, we estimated the surface marker and
cytotoxic function in NK cell of human and showed that the expression of cell cytotoxic related
molecules on NK cells were lower in TCC patient, and the IFN-gamma expressed in NK cells were
also decreased in TCC patients. The cytotoxic function of NK cells from TCC patients was significant
lower than normal control. The survival rate of NK cells from TCC patients after coculture with
lymphoma cell line is also lower. Cocultured NK with Tregs at different ratio before cytotoxic assay
slightly affect cytotoxic function and survival rate both TCC patient or normal control. This session,
we want to investigate interaction between regulatory T cells and NK cytotoxic functions in vivo by
mouse model through subcutaneously injection of MB-49, a bladder cancer cell line, in C57BL/6JNarl
mice. The cytotoxicity and survival rate of mouse NK cells in mouse tumor model had similar
phenotypes with NK cells in human uroepithelium tumor. Furthermore, we want to investigate
whether deplete Treg can enhance antitumor ability by using cyclophosphamide (CTX); an
anti-cancer drug can suppress Treg function in vivo. Only CD4+Foxp3+ cells were decrease in CTX
treated mice while other immune cell populations especially NK cells and CD8+ cells did not affect
by CTX treatment compared with control mice. Furthermore, the proliferation and survival rate of
MB-49 treated with different dosage of CTX did not show difference in vitro, but, in vivo, the tumor
volume in low dose CTX treatment was significantly decreased compared with untreated mice.
Much more, the immunosuppressive ability of Treg cells of CTX treated mice was lower than
untreated mice from day 5 to day 14. Conversely, the cytotoxic function of NK cells after culturing
with IL-2 was increased in CTX treated mice and CTX treated mice repressed NK cells apoptosis much
more than tumor bearing mice. According to our data, we found that Treg cells suppress the
cytotoxic function and enhance apoptosis of NK cells in both human and mice. CTX, deplete Treg
cells only without changing other immune cell populations decrease tumor size and
immunosuppressive function of Treg significantly.