Cytokine Regulation of Natural Killer Receptors in Inhibiting Activated T Cell Function

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2004-07-31

Study Completion Date

2006-12-31

Brief Summary

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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

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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.

Conditions

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Cervical Cancer Breast Cancer Endometrial Cancer Cancer

Keywords

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Cervical cancer Breast cancer T lymphocyte NK receptor

Eligibility Criteria

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Inclusion Criteria

* Cancer patients
* Healthy volunteers

Exclusion Criteria

* Immunosuppression
* HIV carrier

Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Principal Investigators

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Bor-Ching Sheu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Obstetrics and Gynecology, National Taiwan University Hospital

Locations

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National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Bor-Ching Sheu, MD, PhD

Role: CONTACT

Phone: 886-2-2312-3456

Email: [email protected]

Facility Contacts

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Bor-Ching Sheu, MD, PhD

Role: primary

References

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Sheu BC, Chiou SH, Lin HH, Chow SN, Huang SC, Ho HN, Hsu SM. Up-regulation of inhibitory natural killer receptors CD94/NKG2A with suppressed intracellular perforin expression of tumor-infiltrating CD8+ T lymphocytes in human cervical carcinoma. Cancer Res. 2005 Apr 1;65(7):2921-9. doi: 10.1158/0008-5472.CAN-04-2108.

Reference Type RESULT

PMID: 15805295 (View on PubMed)