Format

Send to

Choose Destination
J Biomed Biotechnol. 2010;2010:935764. doi: 10.1155/2010/935764. Epub 2010 Mar 22.

JAK3/STAT5/6 pathway alterations are associated with immune deviation in CD8 T cells in renal cell carcinoma patients.

Author information

1
Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.

Abstract

To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8(+) T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8(+) T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8(+) T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle, was observed. These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8(+) effector cells. If validated, this may define a therapeutic target in the setting of patients with RCC.

PMID:
20339477
PMCID:
PMC2843943
DOI:
10.1155/2010/935764
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Hindawi Limited Icon for PubMed Central
Loading ...
Support Center