6533b871fe1ef96bd12d0bab

RESEARCH PRODUCT

JAK3/STAT5/6 Pathway Alterations Are Associated with Immune Deviation in CD8+ T Cells in Renal Cell Carcinoma Patients

Elisabetta CavalcantiMargherita GiganteVito ManciniMichele BattagliaPasquale DitonnoCarmela CapobiancoRaffaele I. CincioneFrancesco P. SelvaggiWolfgang HerrWalter J. StorkusLoreto GesualdoElena Ranieri

subject

Article SubjectCell Survivallcsh:Biotechnologylcsh:MedicineEnzyme-Linked Immunosorbent AssayE2F4 Transcription FactorCD8-Positive T-Lymphocytesurologic and male genital diseaseslcsh:TP248.13-248.65Chromium IsotopesSTAT5 Transcription FactorTumor Cells CulturedHumansCarcinoma Renal CellInhibitor of Differentiation Protein 2Microscopy Confocallcsh:RCell CycleIntracellular Signaling Peptides and ProteinsJanus Kinase 3Flow Cytometryfemale genital diseases and pregnancy complicationsKidney NeoplasmsGene Expression Regulation NeoplasticCase-Control StudiesLymphocyte Culture Test MixedSTAT6 Transcription FactorCyclin-Dependent Kinase Inhibitor p27Research ArticleSignal Transduction

description

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.

yearjournalcountryeditionlanguage
2010-03-01Journal of Biomedicine and Biotechnology
10.1155/2010/935764http://europepmc.org/articles/PMC2843943