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

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


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.

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Case-Control Studies
  • Cell Cycle
  • Cell Survival
  • Chromium Isotopes
  • Cyclin-Dependent Kinase Inhibitor p27
  • E2F4 Transcription Factor / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitor of Differentiation Protein 2 / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Janus Kinase 3 / metabolism*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Lymphocyte Culture Test, Mixed
  • Microscopy, Confocal
  • STAT5 Transcription Factor / metabolism*
  • STAT6 Transcription Factor / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured


  • CDKN1B protein, human
  • Chromium Isotopes
  • E2F4 Transcription Factor
  • E2F4 protein, human
  • ID2 protein, human
  • Inhibitor of Differentiation Protein 2
  • Intracellular Signaling Peptides and Proteins
  • STAT5 Transcription Factor
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Cyclin-Dependent Kinase Inhibitor p27
  • JAK3 protein, human
  • Janus Kinase 3