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

Elena Ranieri, Elisabetta Cavalcanti, Margherita Gigante, Vito Mancini, Michele Battaglia, Pasquale Ditonno, Carmela Capobianco, Raffaele I. Cincione, Francesco P. Selvaggi, Wolfgang Herr, Walter J. Storkus, Loreto Gesualdo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number935764
JournalJournal of Biomedicine and Biotechnology
Volume2010
DOIs
Publication statusPublished - 2010

    Fingerprint

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Ranieri, E., Cavalcanti, E., Gigante, M., Mancini, V., Battaglia, M., Ditonno, P., Capobianco, C., Cincione, R. I., Selvaggi, F. P., Herr, W., Storkus, W. J., & Gesualdo, L. (2010). JAK3/STAT5/6 pathway alterations are associated with immune deviation in CD8+ T cells in renal cell carcinoma patients. Journal of Biomedicine and Biotechnology, 2010, [935764]. https://doi.org/10.1155/2010/935764