Brief Title
Cytokine Regulation of Natural Killer Receptors in Inhibiting Activated T Cell Function
Brief Summary
In this study proposal, the investigators will extend their previous studies and examine the
kinetic cytotoxic activity with concordant expression of inhibitory natural killer (NK)
receptors (iNKR) on activated T cells. The inhibitory role of cytokines will be defined by
utilizing the investigators' previously established models of mixed lymphocytes and tumor
cells coculture to analyze the expression and activity of cytokines involved in the
regulation of iNKRs on cancer-encountered T cells.
Detailed Description
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.
Study Type
Observational
Condition
Cervical Cancer
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
200
Start Date
July 2004
Completion Date
December 2006
Eligibility Criteria
Inclusion Criteria:
- Cancer patients
- Healthy volunteers
Exclusion Criteria:
- Immunosuppression
- HIV carrier
Gender
Female
Ages
18 Years - 50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Bor-Ching Sheu, MD, PhD, 886-2-2312-3456, [email protected]
Location Countries
Taiwan
Location Countries
Taiwan
Administrative Informations
NCT ID
NCT00173290
Organization ID
9461700613
Secondary IDs
NTUH 94-S045
Study Sponsor
National Taiwan University Hospital
Study Sponsor
Bor-Ching Sheu, MD, PhD, Principal Investigator, Department of Obstetrics and Gynecology, National Taiwan University Hospital
Verification Date
June 2005