In our extended studies, we have directly examined the expressions of various inhibitory
natural killer cell Receptors (iNKRs) on Tumor-infiltrating lymphocytes (TILs) derived from
human Cervical cancer (CC) by triple-color flow cytometry with combination of different
surface markers. We found up-regulated expression of certain iNKRs (CD94/NKG2A) in TILs and
in mixed lymphocyte-cancer cell cocultures. In our previous studies, we demonstrated that
certain cytokines, including IL-10, TGF-beta (Sheu et al, Journal of Immunology, 2001,
167:2972-2978), and IL-15 (Sheu et al, Cancer Research, 2005, 65:2921-2929) can be expressed
by CC cells. We further demonstrated that activated T cells bear iNKRs which inhibit
cytotoxic activity. iNKRs are proposed to restrain the T cell receptor (TCR)-mediated
cytolysis. We found that CC cells had altered HLA-A, -B, and -C molecules in a cancer
microenvironment. The acquisition of both NK-like activity and expression of iNKRs by these
T cells is parallel to prevent damage to normal host cells. However, there is also limited
knowledge about the regulatory role of iNKR expression in T cell cytotoxicity.
Observational
N/A
Bor-Ching Sheu, MD, PhD
Principal Investigator
Department of Obstetrics and Gynecology, National Taiwan University Hospital
Taiwan: Department of Health
9461700613
NCT00173290
July 2004
December 2006
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